{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:14:34Z","timestamp":1792181674683,"version":"4.4.0"},"reference-count":60,"publisher":"Rockefeller University Press","issue":"10","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["323183"],"award-info":[{"award-number":["323183"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["149475"],"award-info":[{"award-number":["149475"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Commission of the European Communities"},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["HEALTH-2011-280873"],"award-info":[{"award-number":["HEALTH-2011-280873"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013850","name":"Helmut Horten Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,5]]},"abstract":"<jats:p>The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry\u2013based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.<\/jats:p>","DOI":"10.1084\/jem.20200206","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T13:20:03Z","timestamp":1594300803000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin"],"prefix":"10.1084","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8674-4294","authenticated-orcid":true,"given":"Antonino","family":"Cassotta","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"},{"name":"Institute of Microbiology, ETH Z\u00fcrich, Z\u00fcrich, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Paparoditis","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-1669","authenticated-orcid":true,"given":"Roger","family":"Geiger","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramgopal R.","family":"Mettu","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Tulane University, New Orleans, LA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-0543","authenticated-orcid":true,"given":"Samuel J.","family":"Landry","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9778-7940","authenticated-orcid":true,"given":"Alessia","family":"Donati","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Benevento","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7538-4262","authenticated-orcid":true,"given":"Mathilde","family":"Foglierini","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"},{"name":"Swiss Institute of Bioinformatics, Lausanne, Switzerland 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Surrey Clinical Research Centre, University of Surrey, Guildford, UK 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lanzavecchia","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-2752","authenticated-orcid":true,"given":"Federica","family":"Sallusto","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine, Universit\u00e0 della Svizzera italiana, Faculty of Biomedical Sciences, Bellinzona, Switzerland 1"},{"name":"Institute of Microbiology, ETH Z\u00fcrich, Z\u00fcrich, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"2023072617202891100_bib1","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.immuni.2019.08.012","article-title":"Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry Enhances Cancer Epitope Prediction","volume":"51","author":"Abelin","year":"2019","journal-title":"Immunity"},{"key":"2023072617202891100_bib2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028852","article-title":"Is It Possible to Develop a \u201cUniversal\u201d Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination","volume":"10","author":"Angeletti","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol"},{"key":"2023072617202891100_bib3","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1074\/mcp.M114.042812","article-title":"Mass spectrometry of human leukocyte antigen class I peptidomes reveals strong effects of protein abundance and turnover on antigen presentation","volume":"14","author":"Bassani-Sternberg","year":"2015","journal-title":"Mol. Cell. Proteomics"},{"key":"2023072617202891100_bib4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/371037a0","article-title":"Structure of influenza haemagglutinin at the pH of membrane fusion","volume":"371","author":"Bullough","year":"1994","journal-title":"Nature"},{"key":"2023072617202891100_bib5","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1084\/jem.189.4.701","article-title":"T cell affinity maturation by selective expansion during infection","volume":"189","author":"Busch","year":"1999","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib6","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1084\/jem.20130555","article-title":"Proteome-wide analysis of HIV-specific naive and memory CD4(+) T cells in unexposed blood donors","volume":"211","author":"Campion","year":"2014","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib7","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1126\/science.1205669","article-title":"A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins","volume":"333","author":"Corti","year":"2011","journal-title":"Science"},{"key":"2023072617202891100_bib8","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","article-title":"Andromeda: a peptide search engine integrated into the MaxQuant environment","volume":"10","author":"Cox","year":"2011","journal-title":"J. Proteome Res"},{"key":"2023072617202891100_bib9","doi-asserted-by":"publisher","first-page":"7922","DOI":"10.1073\/pnas.0501190102","article-title":"Autophagy promotes MHC class II presentation of peptides from intracellular source proteins","volume":"102","author":"Dengjel","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617202891100_bib10","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1128\/JVI.73.2.1411-1418.1999","article-title":"Human parainfluenza virus type 3 up-regulates major histocompatibility complex class I and II expression on respiratory epithelial cells: involvement of a STAT1- and CIITA-independent pathway","volume":"73","author":"Gao","year":"1999","journal-title":"J. Virol"},{"key":"2023072617202891100_bib11","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1084\/jem.20090504","article-title":"Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cells","volume":"206","author":"Geiger","year":"2009","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib12","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1038\/s41591-018-0203-7","article-title":"Antigen discovery and specification of immunodominance hierarchies for MHCII-restricted epitopes","volume":"24","author":"Graham","year":"2018","journal-title":"Nat. Med"},{"key":"2023072617202891100_bib13","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.4049\/jimmunol.1102661","article-title":"The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude","volume":"188","author":"Jenkins","year":"2012","journal-title":"J. Immunol"},{"key":"2023072617202891100_bib14","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/imm.12889","article-title":"Improved methods for predicting peptide binding affinity to MHC class II molecules","volume":"154","author":"Jensen","year":"2018","journal-title":"Immunology"},{"key":"2023072617202891100_bib15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1745-7580-5-2","article-title":"Functional recombinant MHC class II molecules and high-throughput peptide-binding assays","volume":"5","author":"Justesen","year":"2009","journal-title":"Immunome Res"},{"key":"2023072617202891100_bib16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.coi.2014.12.005","article-title":"Determinants of immunodominance for CD4 T cells","volume":"34","author":"Kim","year":"2015","journal-title":"Curr. Opin. Immunol"},{"key":"2023072617202891100_bib17","doi-asserted-by":"publisher","first-page":"8907","DOI":"10.1038\/s41598-017-09331-w","article-title":"Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination","volume":"7","author":"Koblischke","year":"2017","journal-title":"Sci. Rep"},{"key":"2023072617202891100_bib18","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028845","article-title":"Is It Possible to Develop a \u201cUniversal\u201d Influenza Virus Vaccine? Potential Target Antigens and Critical Aspects for a Universal Influenza Vaccine","volume":"10","author":"Krammer","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol"},{"key":"2023072617202891100_bib19","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1128\/JVI.02026-07","article-title":"Three-dimensional structure determines the pattern of CD4+ T-cell epitope dominance in influenza virus hemagglutinin","volume":"82","author":"Landry","year":"2008","journal-title":"J. Virol"},{"key":"2023072617202891100_bib20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41586-018-0540-1","article-title":"T cells in patients with\u00a0narcolepsy target self-antigens of hypocretin neurons","volume":"562","author":"Latorre","year":"2018","journal-title":"Nature"},{"key":"2023072617202891100_bib21","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.chom.2019.01.010","article-title":"Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations","volume":"25","author":"Lee","year":"2019","journal-title":"Cell Host Microbe"},{"key":"2023072617202891100_bib22","first-page":"323","article-title":"Structural characterization of viral epitopes recognized by broadly cross-reactive antibodies","volume":"386","author":"Lee","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol"},{"key":"2023072617202891100_bib23","doi-asserted-by":"publisher","first-page":"D1006","DOI":"10.1093\/nar\/gkn838","article-title":"IMGT, the international ImMunoGeneTics information system","volume":"37","author":"Lefranc","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023072617202891100_bib24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003130","article-title":"Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset","volume":"9","author":"Lindestam Arlehamn","year":"2013","journal-title":"PLoS Pathog"},{"key":"2023072617202891100_bib25","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.immuni.2004.09.008","article-title":"Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties","volume":"21","author":"Malherbe","year":"2004","journal-title":"Immunity"},{"key":"2023072617202891100_bib26","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1084\/jem.189.11.1823","article-title":"Evolution of antigen-specific T cell receptors in vivo: preimmune and antigen-driven selection of preferred complementarity-determining region 3 (CDR3) motifs","volume":"189","author":"McHeyzer-Williams","year":"1999","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib27","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.coi.2013.11.005","article-title":"HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation","volume":"26","author":"Mellins","year":"2014","journal-title":"Curr. Opin. Immunol"},{"key":"2023072617202891100_bib28","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jim.2016.02.013","article-title":"CD4+ T-cell epitope prediction using antigen processing constraints","volume":"432","author":"Mettu","year":"2016","journal-title":"J. Immunol. Methods"},{"key":"2023072617202891100_bib29","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/eji.200738011","article-title":"Antigen structure influences helper T-cell epitope dominance in the human immune response to HIV envelope glycoprotein gp120","volume":"38","author":"Mirano-Bascos","year":"2008","journal-title":"Eur. J. Immunol"},{"key":"2023072617202891100_bib30","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1038\/nri3294","article-title":"Unconventional recognition of peptides by T cells and the implications for autoimmunity","volume":"12","author":"Mohan","year":"2012","journal-title":"Nat. Rev. Immunol"},{"key":"2023072617202891100_bib31","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.immuni.2007.07.007","article-title":"Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude","volume":"27","author":"Moon","year":"2007","journal-title":"Immunity"},{"key":"2023072617202891100_bib32","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.immuni.2014.12.022","article-title":"T cell receptor cross-reactivity between similar foreign and self peptides influences naive cell population size and autoimmunity","volume":"42","author":"Nelson","year":"2015","journal-title":"Immunity"},{"key":"2023072617202891100_bib33","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nature13764","article-title":"Rapid development of broadly influenza neutralizing antibodies through redundant mutations","volume":"516","author":"Pappas","year":"2014","journal-title":"Nature"},{"key":"2023072617202891100_bib34","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jim.2015.03.022","article-title":"Development and validation of a broad scheme for prediction of HLA class II restricted T cell epitopes","volume":"422","author":"Paul","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"2023072617202891100_bib35","doi-asserted-by":"publisher","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: improving support for quantification data","volume":"47","author":"Perez-Riverol","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023072617202891100_bib36","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1146\/annurev.immunol.19.1.331","article-title":"The bare lymphocyte syndrome and the regulation of MHC expression","volume":"19","author":"Reith","year":"2001","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617202891100_bib37","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nri3818","article-title":"The ins and outs of MHC class II-mediated antigen processing and presentation","volume":"15","author":"Roche","year":"2015","journal-title":"Nat. Rev. Immunol"},{"key":"2023072617202891100_bib38","doi-asserted-by":"publisher","first-page":"372","DOI":"10.3389\/fimmu.2015.00372","article-title":"MHC Class II Auto-Antigen Presentation is Unconventional","volume":"6","author":"Sadegh-Nasseri","year":"2015","journal-title":"Front. Immunol"},{"key":"2023072617202891100_bib39","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1084\/jem.179.4.1109","article-title":"Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte\/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha","volume":"179","author":"Sallusto","year":"1994","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib40","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.immuni.2010.10.008","article-title":"From vaccines to memory and back","volume":"33","author":"Sallusto","year":"2010","journal-title":"Immunity"},{"key":"2023072617202891100_bib41","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/j.0105-2896.2005.00307.x","article-title":"The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II:peptide complexes","volume":"207","author":"Sant","year":"2005","journal-title":"Immunol. Rev"},{"key":"2023072617202891100_bib42","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S1074-7613(00)80048-5","article-title":"A kinetic basis for T cell receptor repertoire selection during an immune response","volume":"10","author":"Savage","year":"1999","journal-title":"Immunity"},{"key":"2023072617202891100_bib43","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.immuni.2006.10.018","article-title":"Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes","volume":"26","author":"Schmid","year":"2007","journal-title":"Immunity"},{"key":"2023072617202891100_bib44","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1146\/annurev.iy.11.040193.003501","article-title":"Dominance and crypticity of T cell antigenic determinants","volume":"11","author":"Sercarz","year":"1993","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617202891100_bib45","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1084\/jem.181.6.1957","article-title":"Modulation of antigen processing by bound antibodies can boost or suppress class II major histocompatibility complex presentation of different T cell determinants","volume":"181","author":"Simitsek","year":"1995","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib46","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/163688a0","article-title":"Measurement of Diversity","volume":"163","author":"Simpson","year":"1949","journal-title":"Nature"},{"key":"2023072617202891100_bib47","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1089\/hyb.1983.2.423","article-title":"Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines","volume":"2","author":"Spits","year":"1983","journal-title":"Hybridoma"},{"key":"2023072617202891100_bib48","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.immuni.2012.10.021","article-title":"Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults","volume":"38","author":"Su","year":"2013","journal-title":"Immunity"},{"key":"2023072617202891100_bib49","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/nm1080","article-title":"An efficient method to make human monoclonal antibodies from memory B cells: potent neutralization of SARS coronavirus","volume":"10","author":"Traggiai","year":"2004","journal-title":"Nat. Med"},{"key":"2023072617202891100_bib50","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1146\/annurev-immunol-041015-055420","article-title":"Variations in MHC Class II Antigen Processing and Presentation in Health and Disease","volume":"34","author":"Unanue","year":"2016","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617202891100_bib51","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1186\/1471-2105-11-568","article-title":"Peptide binding predictions for HLA DR, DP and DQ molecules","volume":"11","author":"Wang","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023072617202891100_bib52","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/304358a0","article-title":"Detection of a novel human class II HLA antigen","volume":"304","author":"Watson","year":"1983","journal-title":"Nature"},{"key":"2023072617202891100_bib53","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1084\/jem.178.4.1459","article-title":"Suppressive effect of antibody on processing of T cell epitopes","volume":"178","author":"Watts","year":"1993","journal-title":"J. Exp. Med"},{"key":"2023072617202891100_bib54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/nyas.12462","article-title":"Continuing challenges in influenza","volume":"1323","author":"Webster","year":"2014","journal-title":"Ann. N. Y. Acad. Sci"},{"key":"2023072617202891100_bib55","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1126\/science.1186430","article-title":"Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus","volume":"328","author":"Xu","year":"2010","journal-title":"Science"},{"key":"2023072617202891100_bib56","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.immuni.2006.09.005","article-title":"Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses","volume":"25","author":"Yewdell","year":"2006","journal-title":"Immunity"},{"key":"2023072617202891100_bib57","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev.immunol.17.1.51","article-title":"Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses","volume":"17","author":"Yewdell","year":"1999","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617202891100_bib58","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.immuni.2004.06.015","article-title":"Immunodominance in TCD8+ responses to viruses: cell biology, cellular immunology, and mathematical models","volume":"21","author":"Yewdell","year":"2004","journal-title":"Immunity"},{"key":"2023072617202891100_bib59","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1600-6143.2003.00637.x","article-title":"A renewable source of donor cells for repetitive monitoring of T- and B-cell alloreactivity","volume":"5","author":"Zand","year":"2005","journal-title":"Am. J. Transplant"},{"key":"2023072617202891100_bib60","first-page":"399","article-title":"Memory CD4 T cells in influenza","volume":"386","author":"Zens","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20200206\/1778748\/jem_20200206.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20200206\/1778748\/jem_20200206.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T20:17:01Z","timestamp":1690402621000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/217\/10\/e20200206\/151933\/Deciphering-and-predicting-CD4-T-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":60,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10,5]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20200206","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]},"article-number":"e20200206"}}