{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:15:12Z","timestamp":1788279312693,"version":"build-2803163510"},"reference-count":212,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>IMGT\u00ae, the international information system\u00ae (IMGT), was created in 1989 by Marie-Paule Lefranc (Universit\u00e9 de Montpellier and CNRS) in Montpellier, France, to deal with and to manage the huge diversity of immunoglobulins (IG) or antibodies and T-cell receptors (TR), which are the antigen receptors (AR) of the adaptive immune response (AIR) of jawed vertebrates. The founding of IMGT\u00ae marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. The biocuration of the IMGT data (IG and TR sequences, genes and structures) and the implementation of the IMGT system (7 databases, 17 tools, 25,000 Web resources pages) are based on the IMGT Scientific chart rules (keywords, labels, nomenclature, numbering\u2026) generated from the IMGT-ONTOLOGY axioms and concepts. The IMGT nomenclature (IMGT-NC) and the IMGT unique numbering, the two pillars of immunoinformatics, have been used to define 335 engineered variants for effector properties and formats of therapeutic antibodies (including 12 chimerisotypes) and TR, fusion proteins for immune applications (FPIA) and composite proteins for clinical applications (CPCA). IMGT-NC engineered variant names from the World Health Organization (WHO) International Nonproprietary Name (INN) programme descriptions contribute to the common language for immunoinformatics and artificial intelligence (AI).<\/jats:p>","DOI":"10.3390\/biom16091264","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"1264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IMGT-NC Engineered Variants of INN Therapeutic IG or Antibodies and Related IgSF Proteins (TR, FPIA and CPCA): Bridging Sequences, Structures and Functions for AI"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-9353","authenticated-orcid":false,"given":"Marie-Paule","family":"Lefranc","sequence":"first","affiliation":[{"name":"IMGT<sup>\u00ae<\/sup>, the International ImMunoGeneTics Information System<sup>\u00ae<\/sup> (IMGT), Laboratoire d\u2019ImmunoG\u00e9n\u00e9tique Mol\u00e9culaire (LIGM), Institut de G\u00e9n\u00e9tique Humaine (IGH), Universit\u00e9 de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS), UMR 9002 CNRS-UM, 141 Rue de la Cardonille, CEDEX 5, 34396 Montpellier, France"},{"name":"Institut Universitaire de France, 75231 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","unstructured":"Lefranc, M.-P., and Lefranc, G. (2001). The Immunoglobulin FactsBook, Academic Press."},{"key":"ref_2","unstructured":"Lefranc, M.-P., and Lefranc, G. (2001). The T Cell Receptor FactsBook, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P. (2014). Immunoglobulin and T cell receptor genes: IMGT\u00ae and the birth and rise of immunoinformatics. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00022"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Coligan, J.E., Bierer, B.E., Margulies, D.E., Shevach, E.M., and Strober, W. (2000). Nomenclature of the human immunoglobulin genes. Current Protocols in Immunology, John Wiley and Sons.","DOI":"10.1002\/0471142735"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Coligan, J.E., Bierer, B.E., Margulies, D.E., Shevach, E.M., and Strober, W. (2000). Nomenclature of the human T cell receptor genes. Current Protocols in Immunology, John Wiley and Sons.","DOI":"10.1002\/0471142735"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.3390\/biom4041102","article-title":"Immunoglobulins: 25 years of Immunoinformatics and IMGT-ONTOLOGY","volume":"4","author":"Lefranc","year":"2014","journal-title":"Biomolecules"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P., and Lefranc, G. (2019). IMGT\u00ae and 30 years of immunoinformatics insight in antibody V and C domain structure and function. Antibodies, 8.","DOI":"10.3390\/antib8020029"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P., and Lefranc, G. (2020). Immunoglobulins or antibodies: IMGT bridging genes, structures and functions. Biomedicines, 8.","DOI":"10.3390\/biomedicines8090319"},{"key":"ref_9","unstructured":"Bock, G., and Goode, J. (2003). IMGT, the international ImMunoGeneTics information system\u00ae. Immunoinformatics: Bioinformatic Strate Gies for Better Understanding of Immune Function, John Wiley and Sons. discussion pp. 136\u2013142, 216\u2013222, 250\u2013252."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.molimm.2003.09.006","article-title":"IMGT-ONTOLOGY and IMGT databases, tools and web resources for immunogenetics and immunoinformatics","volume":"40","author":"Lefranc","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bib\/bbn014","article-title":"IMGT, a system and an ontology that bridge biological and computational spheres in bioinformatics","volume":"9","author":"Lefranc","year":"2008","journal-title":"Brief. Bioinform."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Schoenbach, C., Ranganathan, S., and Brusic, V. (2008). IMGT-ONTOLOGY, IMGT\u00ae databases, tools and Web resources for Immunoinformatics. Immunoinformatics, Springer. Chapter 1.","DOI":"10.1007\/978-0-387-72968-8"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12033-008-9062-7","article-title":"IMGT, the international ImMunoGeneTics information system for immunoinformatics. Methods for querying IMGT\u00ae databases, tools and Web resources in the context of immunoinformatics","volume":"40","author":"Lefranc","year":"2008","journal-title":"Mol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1093\/bioinformatics\/15.12.1047","article-title":"Ontology for Immunogenetics: IMGT-ONTOLOGY","volume":"15","author":"Giudicelli","year":"1999","journal-title":"Bioinformatics"},{"key":"ref_15","unstructured":"Hacid, M.-S., Kodratoff, Y., and Boulanger, D. (2023). IMGT-ONTOLOGY: Gestion et d\u00e9couverte de connaissances au sein d\u2019IMGT. Extraction et Gestion des Connaissances (EGC\u20192003), Actes des Troisi\u00e8mes Journ\u00e9es Extraction et Gestion des Connaissances, Lyon, France, 2003, Herm\u00e8s Science Publications Lavoisier. Revue des Sciences et Technologies de l\u2019Information, RSTI, S\u00e9rie Revue d\u2019Intelligence Artificielle-Extraction des Connaissances et Apprentissage (RIA-ECA)."},{"key":"ref_16","first-page":"17","article-title":"IMGT-ONTOLOGY for Immunogenetics and Immunoinformatics","volume":"4","author":"Lefranc","year":"2004","journal-title":"Silico Biol."},{"key":"ref_17","first-page":"45","article-title":"IMGT-Choreography for Immunogenetics and Immunoinformatics","volume":"5","author":"Lefranc","year":"2005","journal-title":"Silico Biol."},{"key":"ref_18","unstructured":"Danos, V., and Schachter, V. (2005). IMGT-Choreography: Processing of complex immunogenetics knowledge. Computational Methods in Systems Biology CMSB 2004, Springer. Lecture Notes in Computer Science."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Keet, C.M., and Franconi, E. (2005). IMGT-ONTOLOGY and IMGT Databases, Tools and Web Resources for Immunoinformatics. From the IMGT Genomics, Genetics and Structural Approaches to IMGT-Choreography. Computer Science and IT with\/for, Biology, Free University of Bozen-Bolzano. Interdisciplinary Seminar Series.","DOI":"10.1016\/j.molimm.2003.09.006"},{"key":"ref_20","unstructured":"Chaume, D., Combres, K., Giudicelli, V., and Lefranc, M.-P. (2005, January 5\u20137). Retrieving factual data and documents using IMGT-ML in the IMGT information system\u00ae. Technologies and technological platforms of interest to the field, with emphasis on: Ontologies, Databases and Applications of Semantics in Bioinformatics. Proceedings of the NETTAB 2005 Workflows Management: New Abilities for the Biological Information Overflow, Naples, Italy."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.biochi.2007.09.003","article-title":"IMGT-Kaleidoscope, the formal IMGT-ONTOLOGY paradigm","volume":"90","author":"Duroux","year":"2008","journal-title":"Biochimie"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Giudicelli, V., and Lefranc, M.-P. (2012). IMGT-ONTOLOGY 2012. Frontiers in Bioinformatics and Computational Biology. Front. Genet., 3.","DOI":"10.3389\/fgene.2012.00079"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dubitzky, W., Wolkenhauer, O., Cho, K.-H., and Yokota, H. (2013). IMGT-ONTOLOGY. Encyclopedia of Systems Biology, Springer Science & Business Media, LLC.","DOI":"10.1007\/978-1-4419-9863-7"},{"key":"ref_24","first-page":"604","article-title":"From IMGT-ONTOLOGY IDENTIFICATION axiom to IMGT standardized keywords: For immunoglobulins (IG), T cell receptors (TR), and conventional genes","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_25","first-page":"614","article-title":"From IMGT-ONTOLOGY DESCRIPTION axiom to IMGT standardized labels: For immunoglobulin (IG) and T cell receptor (TR) sequences and structures","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_26","first-page":"627","article-title":"From IMGT-ONTOLOGY CLASSIFICATION axiom to IMGT standardized gene and allele nomenclature: For immunoglobulins (IG) and T cell receptors (TR)","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0167-5699(97)01163-8","article-title":"Unique database numbering system for immunogenetic analysis","volume":"18","author":"Lefranc","year":"1997","journal-title":"Immunol. Today"},{"key":"ref_28","first-page":"132","article-title":"The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains","volume":"7","author":"Lefranc","year":"1999","journal-title":"Immunologist"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0145-305X(02)00039-3","article-title":"IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains","volume":"27","author":"Lefranc","year":"2003","journal-title":"Dev. Comp. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.dci.2004.07.003","article-title":"IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains","volume":"29","author":"Lefranc","year":"2005","journal-title":"Dev. Comp. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.dci.2005.03.003","article-title":"IMGT unique numbering for MHC groove G-DOMAIN and MHC superfamily (MhcSF) G-LIKE-DOMAIN","volume":"29","author":"Lefranc","year":"2005","journal-title":"Dev. Comp. Immunol."},{"key":"ref_32","first-page":"633","article-title":"IMGT Unique Numbering for the Variable (V), Constant (C), and Groove (G) Domains of IG, TR, MH, IgSF, and MhSF","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dubitzky, W., Wolkenhauer, O., Cho, K.-H., and Yokota, H. (2013). IMGT unique numbering. Encyclopedia of Systems Biology, Springer Science & Business Media, LLC.","DOI":"10.1007\/978-1-4419-9863-7"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-1115-8_4","article-title":"Immunoinformatics of the V, C, and G domains: IMGT\u00ae definitive system for IG, TR and IgSF, MH, and MhSF","volume":"Volume 1184","author":"De","year":"2014","journal-title":"Immunoinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00251-007-0260-4","article-title":"WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors report","volume":"59","author":"Lefranc","year":"2007","journal-title":"Immunogenetics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.dci.2007.09.008","article-title":"WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors report: August 2007, 13th International Congress of Immunology, Rio de Janeiro, Brazil","volume":"32","author":"Lefranc","year":"2008","journal-title":"Dev. Comp. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1038\/s41375-024-02260-4","article-title":"Immunogenetics in hematopathology and hematology: Why a common language is important","volume":"38","author":"Stamatopoulos","year":"2024","journal-title":"Leukemia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-5041-7_1","article-title":"IMGT nomenclature and IMGT unique numbering: The two pillars of 35 years of immunoinformatics for immunoglobulins (IG) or antibodies and T cell receptors (TR)","volume":"2998","author":"Nevoltris","year":"2026","journal-title":"Antibody Engineering"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P., and Lefranc, G. (2026). IMGT\u00ae nomenclature of immunoglobulins (IG) or antibodies and T cell receptors (TR): A common language for immunoinformatics and artificial intelligence (AI). Antibodies, 15.","DOI":"10.3390\/antib15020035"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P., and Lefranc, G. (2022). IMGT\u00ae\u00a0Homo sapiens IG and TR loci, gene order, CNV and haplotypes: New concepts as a paradigm for jawed vertebrates genome assemblies. Biomolecules, 12.","DOI":"10.3390\/biom12030381"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/jmr.647","article-title":"IMGT standardized criteria for statistical analysis of immunoglobulin V-REGION amino acid properties","volume":"17","author":"Levadoux","year":"2004","journal-title":"J. Mol. Recognit."},{"key":"ref_42","unstructured":"Shakib, F. (1990). Molecular genetics of immunoglobin allotype expression. The Human IgG subclasses: Molecular Analysis of Structure, Function and Regulation, Pergamon. Chapter 4."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/978-1-61779-842-9_34","article-title":"Human Gm, Km and Am allotypes and their molecular characterization: A remarkable demonstration of polymorphism","volume":"882","author":"Christiansen","year":"2012","journal-title":"Immunogenetics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3390\/biomedinformatics3030044","article-title":"Human Gm, Km and Am allotypes: WHO\/IMGT nomenclature and IMGT unique numbering for immunoinformatics and therapeutical antibodies","volume":"3","author":"Lefranc","year":"2023","journal-title":"BioMedInformatics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lefranc, M.-P. (2022). IMGT\u00ae nomenclature of engineered IGHG variants involved in antibody effector properties and formats. Antibodies, 11.","DOI":"10.3390\/antib11040065"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/imr.13399","article-title":"Using IMGT unique numbering for IG allotypes and Fc-engineered variants of effector properties and half-life of therapeutic antibodies","volume":"328","author":"Lefranc","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s00251-001-0408-6","article-title":"IMGT gene identification and Colliers de Perles of human immunoglobulins with known 3D structures","volume":"53","author":"Ruiz","year":"2002","journal-title":"Immunogenetics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2174\/157489307779314302","article-title":"IMGT Colliers de Perles: Standardized sequence-structure representations of the IgSF and MhcSF superfamily domains","volume":"2","author":"Kaas","year":"2007","journal-title":"Curr. Bioinform."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/bfgp\/elm032","article-title":"IG, TR and IgSF, MHC and MhcSF: What do we learn from the IMGT Colliers de Perles?","volume":"6","author":"Kaas","year":"2007","journal-title":"Brief. Funct. Genom."},{"key":"ref_50","first-page":"643","article-title":"IMGT Collier de Perles for the variable (V), constant (C), and groove (G) domains of IG, TR, MH, IgSF, and MhSF","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_51","first-page":"726","article-title":"IMGT\/Colliers de Perles: IMGT standardized representation of domains (IG, TR, and IsSF variable and constant domains, MH and MhSF groove domains)","volume":"6","author":"Ehrenmann","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dubitzky, W., Wolkenhauer, O., Cho, K.-H., and Yokota, H. (2013). IMGT Collier de Perles. Encyclopedia of Systems Biology, Springer Science & Business Media, LLC.","DOI":"10.1007\/978-1-4419-9863-7"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D208","DOI":"10.1093\/nar\/gkh042","article-title":"IMGT\/3Dstructure-DB and IMGT\/StructuralQuery, a database and a tool for immunoglobulin, T cell receptor and MHC structural data","volume":"32","author":"Kaas","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"505","DOI":"10.3233\/ISB-00206","article-title":"T cell receptor\/peptide\/MHC molecular characterization and standardized pMHC contact sites in IMGT\/3Dstructure-DB","volume":"5","author":"Kaas","year":"2005","journal-title":"In Silico Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Schoenbach, C., Ranganathan, S., and Brusic, V. (2008). IMGT standardization for molecular characterization of the T cell receptor\/peptide\/MHC complexes. Immunoinformatics, Springer.","DOI":"10.1007\/978-0-387-72968-8"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"D301","DOI":"10.1093\/nar\/gkp946","article-title":"IMGT\/3Dstructure-DB and IMGT\/DomainGapAlign: A database and a tool for immunoglobulins or antibodies, T cell receptors, MHC, IgSF and MhcSF","volume":"38","author":"Ehrenmann","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_57","first-page":"750","article-title":"IMGT\/3Dstructure-DB: Querying the IMGT database for 3D structures in immunology and immunoinformatics (IG or antibodies, TR, MH, RPI, and FPIA)","volume":"6","author":"Ehrenmann","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_58","first-page":"737","article-title":"IMGT\/DomainGapAlign: IMGT standardized analysis of amino acid sequences of variable, constant and groove domains (IG, TR, MH, IgSF, MhSF)","volume":"6","author":"Ehrenmann","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/978-1-61779-842-9_33","article-title":"IMGT\/DomainGapAlign: The IMGT\u00ae tool for the analysis of IG, TR, MHC, IgSF and MhcSF domain amino acid polymorphisms","volume":"882","author":"Christiansen","year":"2012","journal-title":"Immunogenetics"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Marillet, S., Lefranc, M.-P., Boudinot, P., and Cazals, F. (2017). Novel Structural Parameters of Ig-Ag Complexes Yield a Quantitative Description of Interaction Specificity and Binding Affinity. Front Immunol., 8.","DOI":"10.3389\/fimmu.2017.00034"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/978-1-0716-2115-8_25","article-title":"IMGT\/3Dstructure-DB: T-cell receptor TR paratope and peptide\/major histocompatibility pMH contact sites and epitope","volume":"2453","author":"Lefranc","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-2609-2_1","article-title":"Antibody sequence and structure analyses using IMGT\u00ae: 30 years of immunoinformatics","volume":"Volume 2552","author":"Tsumoto","year":"2023","journal-title":"Computer-aided Antibody Design: Methods and Protocols"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"D593","DOI":"10.1093\/nar\/gki065","article-title":"IMGT, the international ImMunoGeneTics information system\u00ae","volume":"33","author":"Lefranc","year":"2005","journal-title":"Nucl. Acids Res."},{"key":"ref_64","first-page":"27","article-title":"IMGT, the international ImMunoGenetics information system\u00ae","volume":"248","author":"Lo","year":"2004","journal-title":"Antibody Engineering Methods and Protocols"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-60327-118-9_2","article-title":"IMGT\u00ae, the international ImMunoGeneTics information system\u00ae for immunoinformatics. Methods for querying IMGT databases, tools and Web resources in the context of immunoinformatics","volume":"Volume 409","author":"Flower","year":"2007","journal-title":"Immunoinformatics: Predicting Immunogenicity In Silico"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D1006","DOI":"10.1093\/nar\/gkn838","article-title":"IMGT, the international ImMunoGeneTics information system","volume":"37","author":"Lefranc","year":"2009","journal-title":"Nucl. Acids Res."},{"key":"ref_67","first-page":"595","article-title":"IMGT, the international ImMunoGeneTics information system","volume":"6","author":"Lefranc","year":"2011","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Dubitzky, W., Wolkenhauer, O., Cho, K.-H., and Yokota, H. (2013). IMGT\u00ae information system. Encyclopedia of Systems Biology, Springer Science & Business Media, LLC.","DOI":"10.1007\/978-1-4419-9863-7"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/microbiolspec.AID-0001-2012","article-title":"Antibody informatics: IMGT\u00ae, the international ImMunoGeneTics information system\u00ae, the international ImMunoGeneTics information system\u00ae","volume":"2","author":"Lefranc","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Crowe, J., Boraschi, D., and Rappuoli, R. (2015). Antibody Informatics: IMGT, the International ImMunoGeneTics Information System. Antibodies for Infectious Diseases, ASM Press.","DOI":"10.1128\/9781555817411"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"D413","DOI":"10.1093\/nar\/gku1056","article-title":"IMGT\u00ae, the international ImMunoGeneTics information system\u00ae 25 years on","volume":"43","author":"Lefranc","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_72","unstructured":"Chouaib, S., and Mencia-Huerta, J.M. (1994). Une base de donn\u00e9es int\u00e9gr\u00e9e en Immunog\u00e9n\u00e9tique, LIGM-DB\/IMGT. L\u2019Immuno-Intervention. De la Bioth\u00e9rapie \u00e0 la Th\u00e9rapie G\u00e9nique, Institut Henri Beaufour."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1749-6632.1995.tb55805.x","article-title":"LIGM-DB\/IMGT: An integrated database of Ig and TcR, part of the Immunogenetics database","volume":"764","author":"Lefranc","year":"1995","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_74","first-page":"59","article-title":"IMGT\/LIGM-DB: A systematized approach for ImMunoGeneTics database coherence and data distribution improvement","volume":"6","author":"Giudicelli","year":"1998","journal-title":"ISMB"},{"key":"ref_75","unstructured":"Chaume, D., Giudicelli, V., and Lefranc, M.-P. (2001). IMGT-ML a XML language for IMGT-ONTOLOGY and IMGT\/LIGM-DB data. CORBA and XML: Towards a Bioinformatics Integrated Network Environment, Proceedings of the NETTAB 2001, Network Tools and Applications in Biology."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"D781","DOI":"10.1093\/nar\/gkj088","article-title":"IMGT\/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences","volume":"34","author":"Giudicelli","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"D256","DOI":"10.1093\/nar\/gki010","article-title":"IMGT\/GENE-DB: A comprehensive database for human and mouse immunoglobulin and T cell receptor genes","volume":"33","author":"Giudicelli","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_78","unstructured":"Poiron, C., Wu, Y., Ginestoux, C., Ehrenmann, F., Duroux, P., and Lefranc, M.-P. (2010, January 7\u20139). IMGT\/mAb-DB: The IMGT\u00ae Database for Therapeutic Monoclonal Antibodies. Proceedings of the 11\u00e8mes Journ\u00e9es Ouvertes de Biologie. Informatique et Math\u00e9matiques (JOBIM) Poster 13, Montpellier, France. Available online: http:\/\/www.jobim2010.fr\/indexe662.html?q=en\/node\/56."},{"key":"ref_79","unstructured":"Giudicelli, C., Alamyar, E., Poiron, C., Ginestoux, C., Duroux, P., and Lefranc, M.-P. (2010, January 5\u20139). IMGT\/HighV-QUEST, IMGT\/DomainGapAlign and IMGT\/mAb-DB: Novel IMGT contribution for antibody engineering and humanization. Proceedings of the Antibody Engineering, IBC 21st Annual International Conference, San Diego, CA, USA."},{"key":"ref_80","unstructured":"Cambon, M., Cherouali, K., Kushwaha, A., Giudicelli, V., Duroux, P., Kossida, S., and Lefranc, M.-P. (2018). IMGT\/mAb-DB and IMGT\/2Dstructure-DB for IMGT standard definition of an antibody: From receptor to amino acid changes. Journ. Ouvert. Biol. Inform. Math. (JOBIM) A, 597."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/mabs.3.1.14151","article-title":"Antibody nomenclature: From IMGT-ONTOLOGY to INN definition","volume":"3","author":"Lefranc","year":"2011","journal-title":"mAbs"},{"key":"ref_82","unstructured":"World Health Organization (2026, July 10). International Nonproprietary Names (INN) for Biological and Biotechnological Substances (a Review). WHO\/EMP\/RHT\/TSN\/2019.1. Available online: http:\/\/www.nihs.go.jp\/dbcb\/INN\/BioReview2019.pdf."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2075078","DOI":"10.1080\/19420862.2022.2075078","article-title":"International nonproprietary names for monoclonal antibodies: An evolving nomenclature system","volume":"14","author":"Thorpe","year":"2022","journal-title":"mAbs"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1084\/jem.173.6.1483","article-title":"The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region","volume":"173","author":"Canfield","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.4049\/jimmunol.147.8.2657","article-title":"Human Fc gamma RI and Fc gamma RII interact with distinct but overlapping sites on human IgG","volume":"147","author":"Lund","year":"1991","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2613::AID-IMMU2613>3.0.CO;2-J","article-title":"Recombinant human IgG molecules lacking Fcgamma receptor I binding and monocyte triggering activities","volume":"29","author":"Armour","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/imr.12482","article-title":"Anti-retroviral antibody FcgammaR-mediated effector functions","volume":"275","author":"Bournazos","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nri.2017.106","article-title":"Beyond binding: Antibody effector functions in infectious diseases","volume":"18","author":"Lu","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Chiu, M.L., Goulet, D.R., Teplyakov, A., and Gilliland, G.L. (2019). Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies, 8.","DOI":"10.3390\/antib8040055"},{"key":"ref_91","first-page":"1","article-title":"IgG Fc Receptors: Evolutionary Considerations","volume":"423","author":"Bournazos","year":"2019","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Liu, R., Oldham, R.J., Teal, E., Beers, S.A., and Cragg, M.S. (2020). Fc-Engineering for Modulated effector functions-improving antibodies for cancer treatment. Antibodies, 9.","DOI":"10.3390\/antib9040064"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41573-022-00501-8","article-title":"Avidity in antibody effector functions and biotherapeutic drug design","volume":"21","author":"Oostindie","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Pejchal, R., Cooper, A.B., Brown, M.E., V\u00e1squez, M., and Krauland, E.M. (2023). Profiling the biophysical developability properties of common IgG1 Fc effector silencing variants. Antibodies, 12.","DOI":"10.3390\/antib12030054"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/978-1-0716-5041-7_15","article-title":"Characterizing pH-dependent interactions between Immunoglobulin and the neonatal Fc Receptor using surface plasmon resonance","volume":"2998","author":"Menant","year":"2026","journal-title":"Methods Mol. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2123299","DOI":"10.1080\/19420862.2022.2123299","article-title":"Systematic analysis of the varied designs of 819 therapeutic antibodies and Fc fusion proteins assigned international nonproprietary names","volume":"14","author":"Wilkinson","year":"2022","journal-title":"mAbs"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2402701","DOI":"10.1080\/19420862.2024.2402701","article-title":"Systematic analysis of Fc mutations designed to reduce binding to Fc-gamma receptors","volume":"16","author":"Hale","year":"2024","journal-title":"mAbs"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2406539","DOI":"10.1080\/19420862.2024.2406539","article-title":"Systematic analysis of Fc mutations designed to enhance binding to Fc-gamma receptors","volume":"16","author":"Hale","year":"2024","journal-title":"mAbs"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/imr.13379","article-title":"Living in LALA land? Forty years of attenuating Fc effector functions","volume":"328","author":"Hale","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1073\/pnas.63.1.78","article-title":"The covalent structure of an entire gammaG immunoglobulin molecule","volume":"63","author":"Edelman","year":"1969","journal-title":"Proc. Natl. Acad. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9036","DOI":"10.1073\/pnas.88.20.9036","article-title":"Identification of the Fc gamma receptor class I binding site in human IgG through the use of recombinant IgG1\/IgG2 hybrid and point-mutated antibodies","volume":"88","author":"Chappel","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6591","DOI":"10.1074\/jbc.M009483200","article-title":"High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R","volume":"276","author":"Shields","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.4049\/jimmunol.164.8.4178","article-title":"Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc","volume":"164","author":"Idusogie","year":"2000","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.4049\/jimmunol.166.4.2571","article-title":"Engineered antibodies with increased activity to recruit complement","volume":"166","author":"Idusogie","year":"2001","journal-title":"J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"12161","DOI":"10.1128\/JVI.75.24.12161-12168.2001","article-title":"Effector function activities of a panel of mutants of a broadly neutralizing antibody against human immunodeficiency virus type 1","volume":"75","author":"Hezareh","year":"2001","journal-title":"J. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1006\/cimm.2000.1617","article-title":"In vitro characterization of five humanized OKT3 effector function variant antibodies","volume":"200","author":"Xu","year":"2000","journal-title":"Cell Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Sampei, Z., Koo, C.X., Teo, F.J., Toh, Y.X., Fukuzawa, T., Gan, S.W., Nambu, T., Ho, A., Honda, K., and Igawa, T. (2023). Complement activation by an anti-dengue\/Zika antibody with impaired Fcgamma receptor binding provides strong efficacy and abrogates risk of antibody-dependent enhancement. Antibodies, 12.","DOI":"10.3390\/antib12020036"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.1073\/pnas.0508123103","article-title":"Engineered antibody Fc variants with enhanced effector function","volume":"103","author":"Lazar","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1016\/j.molimm.2007.10.042","article-title":"Structural characterization of a mutated, ADCC enhanced human Fc fragment","volume":"45","author":"Oganesyan","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8882","DOI":"10.1158\/0008-5472.CAN-07-0696","article-title":"Fc optimization of therapeutic antibodies enhances their ability to kill tumor cells in vitro and controls tumor expansion in vivo via low-affinity activating Fcgamma receptors","volume":"67","author":"Stavenhagen","year":"2007","journal-title":"Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"229","DOI":"10.4161\/mabs.23452","article-title":"Novel asymmetrically engineered antibody Fc variant with superior FcR binding affinity and specificity compared with afucosylated Fc variant","volume":"5","author":"Mimoto","year":"2013","journal-title":"mAbs"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jsb.2016.02.001","article-title":"Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcRIIIa","volume":"194","author":"Ahmed","year":"2016","journal-title":"J. Struct. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1158\/1535-7163.MCT-08-0201","article-title":"Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells","volume":"7","author":"Richards","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/protein\/gzw040","article-title":"Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions","volume":"29","author":"Schlothauer","year":"2016","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4161\/mabs.2.2.11158","article-title":"Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions","volume":"2","author":"Moore","year":"2010","journal-title":"mAbs"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.1248943","article-title":"Complement is activated by IgG hexamers assembled at the cell surface","volume":"343","author":"Diebolder","year":"2014","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5171","DOI":"10.4049\/jimmunol.169.9.5171","article-title":"Increasing the affinity of a human IgG1 for the neonatal Fc receptor: Biological consequences","volume":"169","author":"Woods","year":"2002","journal-title":"J. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23514","DOI":"10.1074\/jbc.M604292200","article-title":"Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn)","volume":"281","author":"Kiener","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6147","DOI":"10.1128\/AAC.01285-13","article-title":"A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults","volume":"57","author":"Robbie","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1074\/jbc.M113.537563","article-title":"Structural insights into neonatal Fc receptor-based recycling mechanisms","volume":"289","author":"Oganesyan","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/nbt1143","article-title":"Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels","volume":"23","author":"Vaccaro","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.4049\/jimmunol.148.11.3461","article-title":"Effect of a single amino acid mutation on the activating and immunosuppressive properties of a \u201chumanized\u201d OKT3 monoclonal antibody","volume":"148","author":"Alegre","year":"1992","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1097\/00007890-199457110-00001","article-title":"A non-activating \u201chumanized\u201d anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo","volume":"57","author":"Alegre","year":"1994","journal-title":"Transplantation"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/nbt.1601","article-title":"Enhanced antibody half-life improves in vivo activity","volume":"28","author":"Zalevsky","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3926","DOI":"10.1016\/j.molimm.2008.06.027","article-title":"Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies","volume":"45","author":"Chu","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"991","DOI":"10.4161\/mabs.28841","article-title":"Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcRIIb and CD19","volume":"6","author":"Szili","year":"2014","journal-title":"mAbs"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/protein\/9.7.617","article-title":"\u2018Knobs-into-holes\u2019 engineering of antibody CH3 domains for heavy chain heterodimerization","volume":"9","author":"Ridgway","year":"1996","journal-title":"Protein Eng."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/eji.1830230216","article-title":"The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties","volume":"23","author":"Bolt","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1042\/bj2590347","article-title":"Aglycosylation of human IgG1 and IgG3 monoclonal antibodies can eliminate recognition by human cells expressing Fc gamma RI and\/or Fc gamma RII receptors","volume":"259","author":"Walker","year":"1989","journal-title":"Biochem J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"896","DOI":"10.4161\/mabs.26436","article-title":"Effects of altered FcR binding on antibody pharmacokinetics in cynomolgus monkeys","volume":"5","author":"Leabman","year":"2013","journal-title":"mAbs"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/jmbi.1997.1116","article-title":"Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library","volume":"270","author":"Atwell","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.1073\/pnas.1203954109","article-title":"Mouse model recapitulating human Fc receptor structural and functional diversity","volume":"109","author":"Smith","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.4049\/jimmunol.143.8.2595","article-title":"Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region","volume":"143","author":"Tao","year":"1989","journal-title":"J. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"15309","DOI":"10.1074\/jbc.M113.537936","article-title":"Selective antibody intervention of Toll-like receptor 4 activation through Fc receptor tethering","volume":"289","author":"Shang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1107\/S0907444908007877","article-title":"Structural characterization of a human Fc fragment engineered for lack of effector functions","volume":"64","author":"Oganesyan","year":"2008","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1016\/S0021-9258(17)41886-2","article-title":"Residue at position 331 in the IgG1 and IgG4 CH2 domains contributes to their differential ability to bind and activate complement","volume":"269","author":"Xu","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ymeth.2013.06.035","article-title":"An engineered Fc variant of an IgG eliminates all immune effector functions via structural perturbations","volume":"65","author":"Vafa","year":"2014","journal-title":"Methods"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1172\/JCI128437","article-title":"Antibodies targeting sialyl Lewis A mediate tumor clearance through distinct effector pathways","volume":"129","author":"Weitzenfeld","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"18709","DOI":"10.1073\/pnas.0606304103","article-title":"Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies","volume":"103","author":"Vaccaro","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.jaci.2020.08.028","article-title":"ARGX-117, a therapeutic complement inhibiting antibody targeting C2","volume":"147","author":"Silence","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.4049\/jimmunol.2000961","article-title":"Glycine 236 in the lower hinge region of human IgG1 differentiates FcR from Complement effector function","volume":"205","author":"Brinkhaus","year":"2020","journal-title":"J. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"109433","DOI":"10.1016\/j.celrep.2021.109433","article-title":"A SARS-CoV-2 neutralizing antibody selected from COVID-19 patients binds to the ACE2-RBD interface and is tolerant to most known RBD mutations","volume":"36","author":"Bertoglio","year":"2021","journal-title":"Cell Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.xphs.2016.12.023","article-title":"An \u201cFc-Silenced\u201d IgG1 format with extended half-life designed for improved stability","volume":"106","author":"Borrok","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1111\/all.15262","article-title":"Anti-KIT monoclonal antibody CDX-0159 induces profound and durable mast cell suppression in a healthy volunteer study","volume":"77","author":"Alvarado","year":"2022","journal-title":"Allergy"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1074\/jbc.M116.748525","article-title":"Engineering an IgG Scaffold Lacking Effector Function with Optimized Developability","volume":"292","author":"Jacobsen","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1021\/bc400490z","article-title":"Production of site-specific antibody-drug conjugates using optimized non-natural amino acids in a cell-free expression system","volume":"25","author":"Zimmerman","year":"2014","journal-title":"Bioconjug. Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1080\/19420862.2015.1007816","article-title":"Improving target cell specificity using a novel monovalent bispecific IgG design","volume":"7","author":"Mazor","year":"2015","journal-title":"mAbs"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2273449","DOI":"10.1080\/19420862.2023.2273449","article-title":"Robust production of monovalent bispecific IgG antibodies through novel electrostatic steering mutations at the CH1-C\u03bb interface","volume":"15","author":"Bagert","year":"2023","journal-title":"mAbs"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Wilkinson, I., Anderson, S., Fry, J., Julien, L.A., Neville, D., Qureshi, O., Watts, G., and Hale, G. (2021). Fc-engineered antibodies with immune effector functions completely abolished. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0260954"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/protein\/gzt022","article-title":"Engineered antibody Fc variant with selectively enhanced Fc\u03b3RIIb binding over both Fc\u03b3RIIa(R131) and Fc\u03b3RIIa(H131)","volume":"26","author":"Mimoto","year":"2013","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_151","unstructured":"Kadono, S., Mimoto, F., Katada, H., Igawa, T., Kuramochi, T., Muraoka, M., Wada, Y., Haraya, K., Miyazaki, T., and Hattori, K. (2025, November 06). 3wjl. Crystal Structure of IIb Selective Fc Variant, Fc(V12), in Complex with FcgRIIb. Available online: https:\/\/www.wwpdb.org\/pdb?id=pdb_00003wjl."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"646","DOI":"10.4161\/mabs.25632","article-title":"Improving biophysical properties of a bispecific antibody scaffold to aid developability: Quality by molecular design","volume":"5","author":"Lario","year":"2013","journal-title":"mAbs"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"14706","DOI":"10.1074\/jbc.M117.793497","article-title":"A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1","volume":"292","author":"Hendriks","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"19637","DOI":"10.1074\/jbc.M110.117382","article-title":"Enhancing antibody Fc heterodimer formation through electrostatic steering effects: Applications to bispecific molecules and monovalent IgG","volume":"285","author":"Gunasekaran","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"546","DOI":"10.4161\/mabs.3.6.18123","article-title":"A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens","volume":"3","author":"Moore","year":"2011","journal-title":"mAbs"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nbt0798-677","article-title":"An efficient route to human bispecific IgG","volume":"16","author":"Merchant","year":"1998","journal-title":"Nat. Biotechnol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/intimm\/13.8.993","article-title":"The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of -globulin in humans","volume":"13","author":"Firan","year":"2001","journal-title":"Int. Immunol."},{"key":"ref_158","unstructured":"Kuramochi, T., Igawa, T., Katada, H., and Hori, Y. (2025, November 06). Anti-Myostatin Antibodies, Polypeptides Containing Variant Fc Regions, and Methods of Use. WO2017\/104783. Available online: https:\/\/patentscope2.wipo.int\/search\/en\/WO2017104783?docId=WO2017104783."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e2068213","DOI":"10.1080\/19420862.2022.2068213","article-title":"Elimination of plasma soluble antigen in cynomolgus monkeys by combining pH-dependent antigen binding and novel Fc engineering","volume":"14","author":"Hori","year":"2022","journal-title":"mAbs"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1073\/pnas.1220145110","article-title":"Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange","volume":"110","author":"Labrijn","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"51037","DOI":"10.18632\/oncotarget.17558","article-title":"Structural basis of a novel heterodimeric Fc for bispecific antibody production","volume":"8","author":"Wei","year":"2017","journal-title":"Oncotarget"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ymeth.2018.10.006","article-title":"A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats","volume":"154","author":"Moore","year":"2019","journal-title":"Methods"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"9745","DOI":"10.1074\/jbc.M117.782433","article-title":"Immunoglobulin domain interface exchange as a platform technology for the generation of Fc heterodimers and bispecific antibodies","volume":"292","author":"Skegro","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"9392","DOI":"10.1074\/jbc.RA119.012335","article-title":"A single mutation increases heavy-chain heterodimer assembly of bispecific antibodies by inducing structural disorderin one homodimer species","volume":"295","author":"Stutz","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0022-1759(96)00215-3","article-title":"Engineering of Fc(1) and Fc(3) from human immunoglobulin G to analyse subclass specificity for staphylococcal protein A","volume":"201","author":"Jendeberg","year":"1997","journal-title":"J. Immunol. Methods"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1158\/1535-7163.MCT-13-0628","article-title":"A heterodimeric Fc-based bispecific antibody simultaneously targeting VEGFR-2 and Met exhibits potent antitumor activity","volume":"12","author":"Choi","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Tam, S.H., McCarthy, S.G., Armstrong, A.A., Somani, S., Wu, S.-J., Liu, X., Gervais, A., Ernst, R., Saro, D., and Decker, R. (2017). Functional, biophysical, and structural characterization of human IgG1 and IgG4 Fc variants with ablated immune functionality. Antibodies, 6.","DOI":"10.3390\/antib6030012"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/imr.13394","article-title":"Enhancing Fc-mediated effector functions of monoclonal antibodies: The example of HexaBodies","volume":"328","author":"Mutis","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jmb.2012.04.020","article-title":"Generating bispecific human IgG1 and IgG2 antibodies from any antibody pair","volume":"420","author":"Strop","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"20167","DOI":"10.1073\/pnas.0809257105","article-title":"Aglycosylated immunoglobulin G1 variants productively engage activating Fc receptors","volume":"105","author":"Sazinsky","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1814583","DOI":"10.1080\/19420862.2020.1814583","article-title":"Engineered Fc-glycosylation switch to eliminate antibody effector function","volume":"12","author":"Zhou","year":"2020","journal-title":"mAbs"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1158\/0008-5472.CAN-07-6297","article-title":"Engineered antibodies of IgG1\/IgG3 mixed isotype with enhanced cytotoxic activities","volume":"68","author":"Natsume","year":"2008","journal-title":"Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/protein\/gzp094","article-title":"SEEDbodies: Fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies","volume":"23","author":"Davis","year":"2010","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.chembiol.2014.10.017","article-title":"IgGA: A \u201ccross-isotype\u201d engineered human Fc antibody domain that displays both IgG-like and IgA-like effector functions","volume":"2","author":"Kelton","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.molimm.2015.02.017","article-title":"Crystal structures of immunoglobulin Fc heterodimers reveal the molecular basis for heterodimer formation","volume":"65","author":"Choi","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"572","DOI":"10.4161\/mabs.1.6.10185","article-title":"IgG2m4, an engineered antibody isotype with reduced Fc function","volume":"1","author":"An","year":"2009","journal-title":"mAbs"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.1074\/jbc.C300470200","article-title":"Engineered human IgG antibodies with longer serum half-lives in primates","volume":"279","author":"Hinton","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1002\/pro.3852","article-title":"Engineering a human IgG2 antibody stable at low pH","volume":"29","author":"Saito","year":"2020","journal-title":"Protein Sci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nbt1344","article-title":"Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria","volume":"25","author":"Rother","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/ncomms1608","article-title":"Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential","volume":"2","author":"Stapleton","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S0161-5890(01)00010-4","article-title":"Lysine 322 in the human IgG3 C(H)2 domain is crucial for antibody dependent complement activation","volume":"37","author":"Thommesen","year":"2000","journal-title":"Mol. Immunol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1084\/jem.178.2.661","article-title":"Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation","volume":"178","author":"Tao","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nbt.1553","article-title":"Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo","volume":"27","author":"Labrijn","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.4049\/jimmunol.1003336","article-title":"Species-specific determinants in the IgG CH3 domain enable Fab-arm exchange by affecting the noncovalent CH3-CH3 interaction strength","volume":"187","author":"Labrijn","year":"2011","journal-title":"J. Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1724751","DOI":"10.1080\/19420862.2020.1724751","article-title":"HX008: A humanized PD-1 blocking antibody with potent antitumor activity and superior pharmacologic properties","volume":"12","author":"Zhang","year":"2020","journal-title":"mAbs"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Armstrong, A.A., and Gilliland, G.L. (2025, November 06). Crystal Structure of Human IgG1-Sigma Fc Fragment. RCSB PDB 2017. Available online: https:\/\/www.wwpdb.org\/pdb?id=pdb_00005w5l.","DOI":"10.2210\/pdb5w5l\/pdb"},{"key":"ref_187","first-page":"49","article-title":"Identification of a novel substitution in the constant region of a gene coding for amyloidogenic kappa1 light chain","volume":"1454","author":"Wally","year":"1999","journal-title":"Biochem Biophys. Acta"},{"key":"ref_188","first-page":"109\u2013119, quiz 120\u2013121","article-title":"Ten years of orthoclone OKT3 (muromonab-CD3): A review","volume":"6","author":"Smith","year":"1996","journal-title":"J. Transpl. Coord. Off. Publ. N. Am. Transpl. Coord. Organ."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/332563a0","article-title":"Localization of the binding site for the human high-affinity Fc receptor on IgG","volume":"332","author":"Duncan","year":"1988","journal-title":"Nature"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/332738a0","article-title":"The binding site for C1q on IgG","volume":"332","author":"Duncan","year":"1988","journal-title":"Nature"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"11187","DOI":"10.1073\/pnas.1019002108","article-title":"Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies","volume":"108","author":"Schaefer","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1080\/19420862.2016.1197457","article-title":"The use of CrossMAb technology for the generation of bi- and multispecific antibodies","volume":"8","author":"Klein","year":"2016","journal-title":"mAbs"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.coche.2018.01.004","article-title":"Emerging trends in bispecific antibody and scaffold protein therapeutics","volume":"19","author":"Verdino","year":"2018","journal-title":"Curr. Opin. Chem. Eng."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.molimm.2015.01.003","article-title":"Alternative molecular formats and therapeutic applications for bispecific antibodies","volume":"67","author":"Spiess","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1080\/19420862.2016.1268307","article-title":"The making of bispecific antibodies","volume":"9","author":"Brinkmann","year":"2017","journal-title":"mAbs"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/protein\/gzy021","article-title":"Variable heavy-variable light domain and Fab-arm CrossMabs with charged residue exchanges to enforce correct light chain assembly","volume":"31","author":"Regula","year":"2018","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2018.08.010","article-title":"Building blocks for bispecific and trispecific antibodies","volume":"154","author":"Wu","year":"2019","journal-title":"Methods"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ymeth.2018.11.008","article-title":"Engineering therapeutic bispecific antibodies using CrossMab technology","volume":"154","author":"Klein","year":"2019","journal-title":"Methods"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1080\/19420862.2019.1661736","article-title":"DuoMab: A novel CrossMab-based IgG-derived antibody format for enhanced antibody-dependent cell-mediated cytotoxicity","volume":"11","author":"Sustmann","year":"2019","journal-title":"mAbs"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ymeth.2018.10.026","article-title":"Bispecific T-cell engagers: Towards understanding variables influencing the in vitro potency and tumor selectivity and their modulation to enhance their efficacy and safety","volume":"154","author":"Ellerman","year":"2019","journal-title":"Methods"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41573-024-00896-6","article-title":"The present and future of bispecific antibodies for cancer therapy","volume":"23","author":"Klein","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2532851","DOI":"10.1080\/19420862.2025.2532851","article-title":"Trispecific SEED antibodies engineered for neutrophil-mediated cell killing","volume":"17","author":"Natale","year":"2025","journal-title":"mAbs"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2613548","DOI":"10.1080\/19420862.2026.2613548","article-title":"The making of multispecific immunoglobulins\u2014A clinical perspective","volume":"18","author":"Brinkmann","year":"2026","journal-title":"mAbs"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1073\/pnas.1810576116","article-title":"Five computational developability guidelines for therapeutic antibody profiling","volume":"116","author":"Raybould","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"102379","DOI":"10.1016\/j.sbi.2022.102379","article-title":"Advances in computational structure-based antibody design","volume":"74","author":"Hummer","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/pro.4205","article-title":"Observed Antibody Space: A diverse database of cleaned, annotated, and translated unpaired and paired antibody sequences","volume":"31","author":"Olsen","year":"2022","journal-title":"Protein Sci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/s41587-024-02469-9","article-title":"AIntibody: An experimentally validated in silico antibody discovery design challenge","volume":"42","author":"Erasmus","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41551-023-01168-1","article-title":"Designing stable humanized antibodies","volume":"8","author":"Hummer","year":"2024","journal-title":"Nat. Biomed. Eng."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Kenlay, H., Dreyer, F.A., Kovaltsuk, A., Miketa, D., Pires, D., and Deane, C.M. (2024). Large scale paired antibody language models. PLoS Comput. Biol., 20.","DOI":"10.1371\/journal.pcbi.1012646"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41587-023-01991-6","article-title":"Perfecting antibodies with language models","volume":"42","author":"Outeiral","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2511220","DOI":"10.1080\/19420862.2025.2511220","article-title":"Computational design of therapeutic antibodies with improved developability: Efficient traversal of binder landscapes and rescue of escape mutations","volume":"17","author":"Dreyer","year":"2025","journal-title":"mAbs"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Vogt, Y., Ro\u00dfberg, R., Habermann, J., Kluge, P., Xu, W., Naouar, M., Hirschberg, S., Miething, C., B\u00f6decker, J., and Kalweit, M. (2026). Analysing open-source protein folding models for nanobody binding prediction. Front. Bioinform., 6.","DOI":"10.3389\/fbinf.2026.1858891"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:17:09Z","timestamp":1788275829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":212,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091264"],"URL":"https:\/\/doi.org\/10.3390\/biom16091264","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}