{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:00:01Z","timestamp":1777611601501,"version":"3.51.4"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T00:00:00Z","timestamp":1439424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0135451","type":"journal-article","created":{"date-parts":[[2015,8,13]],"date-time":"2015-08-13T14:13:32Z","timestamp":1439475212000},"page":"e0135451","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Predicting Hemagglutinin MHC-II Ligand Analogues in Anti-TNF\u03b1 Biologics: Implications for Immunogenicity of Pharmaceutical Proteins"],"prefix":"10.1371","volume":"10","author":[{"given":"Benjamin J.","family":"Andrick","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra I.","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna","family":"Cauley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren A.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson S.","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,8,13]]},"reference":[{"issue":"2","key":"ref1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1159\/000236718","article-title":"New directions for biological therapy in rheumatoid arthritis","volume":"104","author":"MJ Elliott","year":"1994","journal-title":"Int Arch Allergy Immunol"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.pharmthera.2007.10.001","article-title":"Tumor necrosis factor antagonist mechanisms of action: a comprehensive review","volume":"117","author":"D Tracey","year":"2008","journal-title":"Pharmacology & therapeutics"},{"issue":"7","key":"ref3","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1136\/annrheumdis-2011-150573","article-title":"A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: results from the US CORRONA registry","volume":"71","author":"JD Greenberg","year":"2012","journal-title":"Annals of the rheumatic diseases"},{"issue":"4","key":"ref4","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/art.30207","article-title":"Is there a need for immunopharmacologic guidance of anti\u2013tumor necrosis factor therapies?","volume":"63","author":"K Bendtzen","year":"2011","journal-title":"Arthritis & Rheumatism"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.coi.2008.06.011","article-title":"Immunogenicity of anti-tumor necrosis factor antibodies\u2014toward improved methods of anti-antibody measurement","volume":"20","author":"L Aarden","year":"2008","journal-title":"Current opinion in immunology"},{"issue":"19","key":"ref6","doi-asserted-by":"crossref","first-page":"13799","DOI":"10.1074\/jbc.M112.433961","article-title":"Structural basis for treating tumor necrosis factor alpha (TNFalpha)-associated diseases with the therapeutic antibody infliximab","volume":"288","author":"S Liang","year":"2013","journal-title":"J Biol Chem"},{"issue":"12","key":"ref7","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1002\/art.22214","article-title":"Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab","volume":"54","author":"K Bendtzen","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/art.21671","article-title":"Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis","volume":"54","author":"GJ Wolbink","year":"2006","journal-title":"Arthritis & Rheumatism"},{"key":"ref9","unstructured":"Kaymakcalan Z, Xiong L. Compositions and methods comprising binding proteins for adalimumab. Google Patents; 2008."},{"issue":"14","key":"ref10","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1001\/jama.2011.406","article-title":"Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up","volume":"305","author":"GM Bartelds","year":"2011","journal-title":"Jama"},{"issue":"4","key":"ref11","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1136\/ard.2008.089979","article-title":"Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis","volume":"68","author":"MK de Vries","year":"2009","journal-title":"Ann Rheum Dis"},{"issue":"10","key":"ref12","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s10067-013-2336-x","article-title":"Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNF\u03b1 biologics in rheumatic diseases","volume":"32","author":"C Mok","year":"2013","journal-title":"Clinical rheumatology"},{"issue":"1","key":"ref13","first-page":"40","article-title":"The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis","volume":"25","author":"RK Dore","year":"2007","journal-title":"Clin Exp Rheumatol"},{"issue":"11","key":"ref14","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.it.2007.07.011","article-title":"Immunogenicity of protein therapeutics","volume":"28","author":"AS De Groot","year":"2007","journal-title":"Trends Immunol"},{"issue":"12","key":"ref15","doi-asserted-by":"crossref","first-page":"R63","DOI":"10.1172\/JCI8476","article-title":"MHC class II tetramers identify peptide-specific human CD4&lt; sup&gt;+ T cells proliferating in response to influenza A antigen","volume":"104","author":"EJ Novak","year":"1999","journal-title":"The Journal of clinical investigation"},{"key":"ref16","first-page":"493","article-title":"Adverse Drug Reactions","author":"J Li","year":"2010"},{"issue":"9","key":"ref17","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/rheumatology\/kel054","article-title":"Lack of efficacy of a third tumour necrosis factor alpha antagonist after failure of a soluble receptor and a monoclonal antibody","volume":"45","author":"E Solau-Gervais","year":"2006","journal-title":"Rheumatology (Oxford)"},{"issue":"12","key":"ref18","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1093\/rheumatology\/kem261","article-title":"Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies","volume":"46","author":"M Svenson","year":"2007","journal-title":"Rheumatology (Oxford)"},{"issue":"7","key":"ref19","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1056\/NEJMoa020888","article-title":"Influence of immunogenicity on the long-term efficacy of infliximab in Crohn&apos;s disease","volume":"348","author":"F Baert","year":"2003","journal-title":"N Engl J Med"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1208\/s12248-013-9497-z","article-title":"Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug antibody induction: analysis of human clinical study data for multiple biotherapeutics","volume":"15","author":"L Xue","year":"2013","journal-title":"AAPS J"},{"issue":"2","key":"ref21","doi-asserted-by":"crossref","first-page":"e89442","DOI":"10.1371\/journal.pone.0089442","article-title":"The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNF\u03b1 agent treatment in patients with rheumatoid arthritis: a meta-analysis","volume":"9","author":"Q Lv","year":"2014","journal-title":"PloS one"},{"key":"ref22","doi-asserted-by":"crossref","DOI":"10.1038\/srep01698","article-title":"Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure","volume":"3","author":"SS Huang","year":"2013","journal-title":"Scientific reports"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"e00150","DOI":"10.1128\/mBio.00150-11","article-title":"Why do influenza virus subtypes die out? A hypothesis","volume":"2","author":"P Palese","year":"2011","journal-title":"MBio"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1056\/NEJMra0904322","article-title":"Historical perspective\u2014emergence of influenza A (H1N1) viruses","volume":"361","author":"SM Zimmer","year":"2009","journal-title":"New England Journal of Medicine"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1473-3099(07)70029-4","article-title":"Transmission of influenza A in human beings","volume":"7","author":"G Brankston","year":"2007","journal-title":"The Lancet infectious diseases"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis","volume":"44","author":"S Raychaudhuri","year":"2012","journal-title":"Nat Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/1471-2105-10-296","article-title":"NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction","volume":"10","author":"M Nielsen","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/1471-2105-8-238","article-title":"Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method","volume":"8","author":"M Nielsen","year":"2007","journal-title":"BMC Bioinformatics"},{"issue":"6","key":"ref29","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/9858","article-title":"Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices","volume":"17","author":"T Sturniolo","year":"1999","journal-title":"Nat Biotechnol"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","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":"P Wang","year":"2010","journal-title":"BMC bioinformatics"},{"issue":"7","key":"ref31","doi-asserted-by":"crossref","first-page":"e1000107","DOI":"10.1371\/journal.pcbi.1000107","article-title":"Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan","volume":"4","author":"M Nielsen","year":"2008","journal-title":"PLoS computational biology"},{"key":"ref32","doi-asserted-by":"crossref","DOI":"10.1137\/1.9780898717648","article-title":"Insight through computing: a MATLAB introduction to computational science and engineering","author":"CF Van Loan","year":"2010"},{"issue":"38","key":"ref33","doi-asserted-by":"crossref","first-page":"27059","DOI":"10.1074\/jbc.M113.491530","article-title":"Comparison of the inhibition mechanisms of adalimumab and infliximab in treating tumor necrosis factor alpha-associated diseases from a molecular view","volume":"288","author":"S Hu","year":"2013","journal-title":"J Biol Chem"},{"key":"ref34","unstructured":"Osslund TD, Clogston CL, Crampton SL, Bass RB. Crystals of etanercept and methods of making thereof. Google Patents; 2007."},{"issue":"21","key":"ref35","doi-asserted-by":"crossref","first-page":"5611","DOI":"10.1093\/emboj\/19.21.5611","article-title":"Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1","volume":"19","author":"J Hennecke","year":"2000","journal-title":"Embo j"},{"issue":"10","key":"ref36","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/ni835","article-title":"A functional and structural basis for TCR cross-reactivity in multiple sclerosis","volume":"3","author":"HL Lang","year":"2002","journal-title":"Nature immunology"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jneuroim.2013.12.009","article-title":"A molecular view of multiple sclerosis and experimental autoimmune encephalitis: What can we learn from the epitope data?","volume":"267","author":"K Vaughan","year":"2014","journal-title":"Journal of neuroimmunology"},{"issue":"09","key":"ref38","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1110\/ps.9.9.1838","article-title":"Structure-based prediction of binding peptides to MHC class I molecules: application to a broad range of MHC alleles","volume":"9","author":"O Schueler-Furman","year":"2000","journal-title":"Protein Science"},{"key":"ref39","article-title":"Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide","author":"LJ Stern","year":"1994","journal-title":"Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nri1805","article-title":"MHC class II proteins and disease: a structural perspective","volume":"6","author":"EY Jones","year":"2006","journal-title":"Nature Reviews Immunology"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"e1000024","DOI":"10.1371\/journal.pgen.1000024","article-title":"Defining the role of the MHC in autoimmunity: a review and pooled analysis","volume":"4","author":"MM Fernando","year":"2008","journal-title":"PLoS genetics"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.autrev.2012.08.017","article-title":"Tregitope update: mechanism of action parallels IVIg","volume":"12","author":"LP Cousens","year":"2013","journal-title":"Autoimmun Rev"},{"issue":"Suppl 1","key":"ref43","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1007\/s10875-012-9762-4","article-title":"In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity","volume":"33","author":"LP Cousens","year":"2013","journal-title":"J Clin Immunol"},{"issue":"17","key":"ref44","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.1016\/j.vaccine.2011.02.019","article-title":"Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4(+) T cells against the swine-origin H1N1 influenza virus","volume":"29","author":"BC Schanen","year":"2011","journal-title":"Vaccine"},{"issue":"3","key":"ref45","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/ana.410340313","article-title":"The T-cell response to myelin basic protein in familial multiple sclerosis: Diversity of fine specificity, restricting elements, and T-cell receptor usage","volume":"34","author":"N Joshi","year":"1993","journal-title":"Annals of neurology"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0165-5728(95)00041-Y","article-title":"In vivo clonal expansion of T lymphocytes specific for an immunodominant N-terminal myelin basic protein epitope in healthy individuals","volume":"59","author":"A Shanmugam","year":"1995","journal-title":"Journal of neuroimmunology"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/0161-5890(93)90121-Q","article-title":"Influence of the T-helper epitope on the titre and affinity of antibodies to B-cell epitopes after co-immunization","volume":"30","author":"DM Shaw","year":"1993","journal-title":"Molecular immunology"},{"issue":"2","key":"ref48","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1365-2567.1996.tb00015.x","article-title":"Immunogenicity of peptides coupled with multiple T-cell epitopes of a surface protein antigen of Streptococcus mutans","volume":"88","author":"H Senpuku","year":"1996","journal-title":"Immunology"},{"issue":"8","key":"ref49","doi-asserted-by":"crossref","first-page":"e23374","DOI":"10.1371\/journal.pone.0023374","article-title":"Identification of a highly conserved H1 subtype-specific epitope with diagnostic potential in the hemagglutinin protein of influenza A virus","volume":"6","author":"R Zhao","year":"2011","journal-title":"PloS one"},{"key":"ref50","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/386148","article-title":"Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine","volume":"2014","author":"CI Da\u00efen","year":"2014","journal-title":"Mediators of inflammation"},{"issue":"6","key":"ref51","doi-asserted-by":"crossref","first-page":"R199","DOI":"10.1186\/ar4389","article-title":"Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity","volume":"15","author":"JM Davis","year":"2013","journal-title":"Arthritis Res Ther"},{"issue":"1","key":"ref52","doi-asserted-by":"crossref","first-page":"R24","DOI":"10.1186\/ar3706","article-title":"A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis","volume":"14","author":"JM Davis 3rd","year":"2012","journal-title":"Arthritis Res Ther"},{"issue":"8","key":"ref53","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.it.2009.05.005","article-title":"Infections and autoimmunity--friends or foes?","volume":"30","author":"S Kivity","year":"2009","journal-title":"Trends Immunol"},{"issue":"1","key":"ref54","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s12016-011-8294-7","article-title":"Molecular mimicry as a mechanism of autoimmune disease","volume":"42","author":"MF Cusick","year":"2012","journal-title":"Clinical reviews in allergy & immunology"},{"issue":"3 Pt 2","key":"ref55","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1006\/clin.1996.0146","article-title":"The pathogenesis of postinfectious myocarditis","volume":"80","author":"NR Rose","year":"1996","journal-title":"Clin Immunol Immunopathol"},{"issue":"4","key":"ref56","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2265.1980.tb02723.x","article-title":"Coxsackie B virus antibody responses in juvenile-onset diabetes mellitus","volume":"12","author":"CG Ray","year":"1980","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1749-6632.2009.04754.x","article-title":"Exposure to Epstein-Barr virus infection is associated with mild systemic lupus erythematosus disease","volume":"1173","author":"G Zandman-Goddard","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.2741\/4010","article-title":"Cross-reactivity of autoreactive T cells with MBP and viral antigens in patients with MS","volume":"17","author":"W Cheng","year":"2012","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"5","key":"ref59","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/0092-8674(95)90348-8","article-title":"Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein","volume":"80","author":"KW Wucherpfennig","year":"1995","journal-title":"Cell"},{"issue":"6","key":"ref60","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrd2307","article-title":"The FDA&apos;s assessment of follow-on protein products: a historical perspective","volume":"6","author":"J Woodcock","year":"2007","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"ref61","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.4049\/jimmunol.174.6.3187","article-title":"Rationally engineered therapeutic proteins with reduced immunogenicity","volume":"174","author":"S Tangri","year":"2005","journal-title":"J Immunol"},{"issue":"12","key":"ref62","doi-asserted-by":"crossref","first-page":"e15877","DOI":"10.1371\/journal.pone.0015877","article-title":"Structural properties of MHC class II ligands, implications for the prediction of MHC class II epitopes","volume":"5","author":"KW J\u00f8rgensen","year":"2010","journal-title":"PloS one"},{"issue":"9","key":"ref63","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0167-5699(98)01299-7","article-title":"A very high level of crossreactivity is an essential feature of the T-cell receptor","volume":"19","author":"D Mason","year":"1998","journal-title":"Immunology today"},{"issue":"6","key":"ref64","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1023\/B:PHAM.0000029275.41323.a6","article-title":"Structure-immunogenicity relationships of therapeutic proteins","volume":"21","author":"S Hermeling","year":"2004","journal-title":"Pharmaceutical research"},{"issue":"Suppl 1","key":"ref65","doi-asserted-by":"crossref","first-page":"i72","DOI":"10.1136\/ard.2009.117564","article-title":"Can we prevent immunogenicity of human protein drugs?","volume":"69","author":"DW Scott","year":"2010","journal-title":"Ann Rheum Dis"},{"issue":"3","key":"ref66","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.clim.2013.09.006","article-title":"T-cell dependent immunogenicity of protein therapeutics: Preclinical assessment and mitigation","volume":"149","author":"V Jawa","year":"2013","journal-title":"Clin Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0135451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T06:05:07Z","timestamp":1540015507000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0135451"}},"subtitle":[],"editor":[{"given":"Yoshihiko","family":"Hoshino","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,8,13]]},"references-count":66,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2015,8,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0135451","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,13]]}}}