{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:54:27Z","timestamp":1791370467220,"version":"4.3.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":263,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000870","name":"Pirbright Institute\u2019s Strategic Programme Grants","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000870","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ISPGs","award":["BBS\/E\/PI\/230001A"],"award-info":[{"award-number":["BBS\/E\/PI\/230001A"]}]},{"name":"ISPGs","award":["BBS\/E\/PI\/230001C"],"award-info":[{"award-number":["BBS\/E\/PI\/230001C"]}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BBS\/E\/PI\/23NB0003"],"award-info":[{"award-number":["BBS\/E\/PI\/23NB0003"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BBS\/E\/PI\/23NB0004"],"award-info":[{"award-number":["BBS\/E\/PI\/23NB0004"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1215550"],"award-info":[{"award-number":["OPP1215550"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pirbright Livestock Antibody Hub"},{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"name":"(CAMS) Innovation Fund for Medical Science"},{"name":"CIFMS","award":["2024-I2M-2-001-1"],"award-info":[{"award-number":["2024-I2M-2-001-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antibody fragment crystallizable (Fc)\u2013mediated effector functions and pharmacokinetics are governed by interactions between immunoglobulin G (IgG) subclasses and Fc gamma receptors (Fc\u03b3Rs) and Fc neonatal receptor (FcRn). Although pigs are increasingly used as translational models for therapeutic antibody evaluation, the interactions between porcine Fc receptors (pFc\u03b3Rs) and porcine (pIgG) or human IgG (hIgG) subclasses remain poorly defined. Here, we characterized the interactions of pIgG and hIgG subclasses with pFc\u03b3Rs and pFcRn and assessed their ability to mediate Fc-dependent effector functions in porcine immune cells. Using biolayer interferometry, we demonstrated subclass-dependent differences in receptor binding, driven primarily by dissociation kinetics. Porcine IgG2 and pIgG5c exhibited stable Fc\u03b3R interactions, whereas pIgG3 and pIgG5b showed weak binding to several low-affinity receptors (Fc\u03b3RIIa, Fc\u03b3RIIb, and Fc\u03b3RIIIa). Human IgG subclasses displayed distinct binding profiles to pFc\u03b3Rs, with hIgG3 showing the strongest and hIgG2 the weakest binding affinity. Furthermore, hIgG1 and hIgG4 did not bind to pFc\u03b3RIIIa. Functional studies demonstrated that hIgGs mediate Fc-dependent phagocytosis and natural killer cell degranulation, although receptor-binding affinity did not always correlate with functional activity. Comparative phylogenetic and functional analyses further revealed that Fc\u03b3R-binding phenotypes are only partially predicted by Fc domain sequence similarity. All pIgG and hIgG subclasses interacted with pFcRn in a comparable pH-dependent manner. These findings demonstrate substantial, but incomplete, conservation of Fc biology between humans and pigs. While supporting the use of pigs as a translational model for antibody pharmacokinetic studies, they also indicate the need for integrated biophysical, structural, and functional analyses before extrapolating Fc-mediated therapeutic activity between species.<\/jats:p>","DOI":"10.1093\/discim\/kyag018","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:02:34Z","timestamp":1789473754000},"source":"Crossref","is-referenced-by-count":0,"title":["Human and porcine IgG subclasses differentially engage porcine Fc receptors"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-4266","authenticated-orcid":false,"given":"Ashutosh","family":"Vats","sequence":"first","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"May","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Moorhouse","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Lokhman","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Crossley","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Hay","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Bonnet-Di Placido","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P","family":"Graham","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramila","family":"Rijal","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Science Oxford Institute, Nuffield Department of Medicine, University of Oxford , Oxford ,","place":["UK"]},{"name":"MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Townsend","sequence":"additional","affiliation":[{"name":"Chinese Academy of Medical Science Oxford Institute, Nuffield Department of Medicine, University of Oxford , Oxford ,","place":["UK"]},{"name":"MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford , Oxford ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Mwangi","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C","family":"Schwartz","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danish","family":"Munir","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Hammond","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elma","family":"Tchilian","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6068-019X","authenticated-orcid":false,"given":"Basudev","family":"Paudyal","sequence":"additional","affiliation":[{"name":"The Pirbright Institute Host Response, , Woking ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"2026100706314082600_kyag018-B1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/imr.12350","article-title":"Mouse and human FcR effector functions","volume":"268","author":"Bruhns","year":"2015","journal-title":"Immunol 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immunization","volume":"188","author":"Langlet","year":"2012","journal-title":"J Immunol"},{"key":"2026100706314082600_kyag018-B5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00251-018-01099-1","article-title":"The genomic organization and expression pattern of the low-affinity Fc gamma receptors (Fc\u03b3R) in the G\u00f6ttingen minipig","volume":"71","author":"Egli","year":"2019","journal-title":"Immunogenetics"},{"key":"2026100706314082600_kyag018-B6","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.MCHD-0045-2016","article-title":"The role and function of Fc\u03b3 receptors on myeloid cells","volume":"4","author":"Bournazos","year":"2016","journal-title":"Microbiol Spectr"},{"key":"2026100706314082600_kyag018-B7","doi-asserted-by":"crossref","first-page":"243","DOI":"10.4161\/mabs.4.2.19387","article-title":"Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration","volume":"4","author":"Zheng","year":"2012","journal-title":"MAbs"},{"key":"2026100706314082600_kyag018-B8","doi-asserted-by":"crossref","first-page":"648","DOI":"10.4049\/jimmunol.2000429","article-title":"Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms","volume":"205","author":"McNee","year":"2020","journal-title":"Journal of Immunology"},{"key":"2026100706314082600_kyag018-B9","doi-asserted-by":"crossref","first-page":"1471412","DOI":"10.3389\/fimmu.2024.1471412","article-title":"Comparative pharmacokinetics of porcine and human anti-influenza hemagglutinin monoclonal antibodies in outbred pigs and minipigs","volume":"15","author":"Paudyal","year":"2024","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/s41541-025-01277-9","article-title":"Aerosol and intranasal delivery of monoclonal antibodies to prevent transmission in pig influenza infection models","volume":"10","author":"Hatton","year":"2025","journal-title":"NPJ Vaccines"},{"key":"2026100706314082600_kyag018-B11","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41577-026-01315-0","article-title":"Why pigs might help US develop better vaccines and drugs against influenza virus","volume":"26","author":"Driver","year":"2026","journal-title":"Nat Rev Immunol"},{"key":"2026100706314082600_kyag018-B12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s11095-019-2574-y","article-title":"The binding of human IgG to minipig Fc\u03b3Rs - implications for preclinical assessment of therapeutic antibodies","volume":"36","author":"Egli","year":"2019","journal-title":"Pharm Res"},{"key":"2026100706314082600_kyag018-B13","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1007\/s10875-012-9782-0","article-title":"Of mice and men: the need for humanized mouse models to study human IgG activity in vivo","volume":"33 Suppl 1","author":"Lux","year":"2013","journal-title":"J Clin Immunol"},{"key":"2026100706314082600_kyag018-B14","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.immuni.2005.11.010","article-title":"Fcgamma receptors: old friends and new family members","volume":"24","author":"Nimmerjahn","year":"2006","journal-title":"Immunity"},{"key":"2026100706314082600_kyag018-B15","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.4049\/jimmunol.172.2.1203","article-title":"Identification of a novel Fc gamma RIIIa alpha-associated molecule that contains significant homology to porcine cathelin","volume":"172","author":"Sweeney","year":"2004","journal-title":"J Immunol"},{"key":"2026100706314082600_kyag018-B16","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nri2155","article-title":"Fcrn: the neonatal Fc receptor comes of age","volume":"7","author":"Roopenian","year":"2007","journal-title":"Nat Rev 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Immunol"},{"key":"2026100706314082600_kyag018-B20","doi-asserted-by":"crossref","first-page":"1286903","DOI":"10.3389\/fimmu.2023.1286903","article-title":"Distinct effector functions mediated by Fc regions of bovine IgG subclasses and their interaction with Fc gamma receptors","volume":"14","author":"Noble","year":"2023","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B21","doi-asserted-by":"crossref","first-page":"e1009330","DOI":"10.1371\/journal.ppat.1009330","article-title":"Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans","volume":"17","author":"Holzer","year":"2021","journal-title":"PLoS Pathog"},{"key":"2026100706314082600_kyag018-B22","doi-asserted-by":"crossref","first-page":"790918","DOI":"10.3389\/fimmu.2021.790918","article-title":"Low dose pig anti-influenza virus monoclonal antibodies reduce lung pathology but do not prevent virus shedding","volume":"12","author":"Paudyal","year":"2021","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B23","doi-asserted-by":"crossref","first-page":"e2406192121","DOI":"10.1073\/pnas.2406192121","article-title":"Complement activation by IgG subclasses is governed by their ability to oligomerize upon antigen binding","volume":"121","author":"Frischauf","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026100706314082600_kyag018-B24","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fc\u03b3 receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"2026100706314082600_kyag018-B25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2206","article-title":"Fc\u03b3 receptors as regulators of immune responses","volume":"8","author":"Nimmerjahn","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2026100706314082600_kyag018-B26","doi-asserted-by":"crossref","first-page":"1838862","DOI":"10.3389\/fimmu.2026.1838862","article-title":"Revised porcine IgG subclass classification based on innate immune cell activation","volume":"17","author":"Van der Weken","year":"2026","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B27","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jconrel.2018.07.023","article-title":"Cellular recycling-driven in vivo half-life extension using recombinant albumin fusions tuned for neonatal Fc receptor (FcRn) engagement","volume":"287","author":"Larsen","year":"2018","journal-title":"J Control Release"},{"key":"2026100706314082600_kyag018-B28","doi-asserted-by":"crossref","first-page":"865","DOI":"10.3389\/fimmu.2018.00865","article-title":"Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors","volume":"9","author":"Morgan","year":"2018","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B29","doi-asserted-by":"crossref","first-page":"e0219999","DOI":"10.1371\/journal.pone.0219999","article-title":"Binding affinities of human IgG1 and chimerized pig and rabbit derivatives to human, pig and rabbit Fc gamma receptor IIIA","volume":"14","author":"Bhatti","year":"2019","journal-title":"PLoS One"},{"key":"2026100706314082600_kyag018-B30","doi-asserted-by":"crossref","first-page":"987151","DOI":"10.3389\/fimmu.2022.987151","article-title":"Role of N-glycosylation in Fc\u03b3RIIIa interaction with IgG","volume":"13","author":"Van Coillie","year":"2022","journal-title":"Front Immunol"},{"key":"2026100706314082600_kyag018-B31","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3389\/fimmu.2020.00740","article-title":"Fc\u03b3r binding and ADCC activity of human IgG allotypes","volume":"11","author":"de 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Pharmacokinet"},{"key":"2026100706314082600_kyag018-B41","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1172\/JCI81104","article-title":"Focused antibody response to influenza linked to antigenic drift","volume":"125","author":"Huang","year":"2015","journal-title":"J Clin Invest"},{"key":"2026100706314082600_kyag018-B42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41541-026-01427-7","article-title":"Cattle antibodies identify a cross-serotype broadly neutralising foot-and-mouth disease virus epitope","volume":"11","author":"Bonnet-Di Placido","year":"2026","journal-title":"npj Vaccines"},{"key":"2026100706314082600_kyag018-B43","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00251-024-01355-7","article-title":"A genome assembly and transcriptome atlas of the inbred Babraham pig to illuminate porcine immunogenetic 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Doremalen","year":"2021","journal-title":"Sci Transl Med"}],"container-title":["Discovery 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