{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:31:33Z","timestamp":1791228693119,"version":"4.1.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T00:00:00Z","timestamp":1440028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hum Genet"],"published-print":{"date-parts":[[2015,11]]},"DOI":"10.1038\/jhg.2015.100","type":"journal-article","created":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T06:20:53Z","timestamp":1440051653000},"page":"697-702","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Associations of human leukocyte antigens with autoimmune diseases: challenges in identifying the mechanism"],"prefix":"10.1038","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6805-414X","authenticated-orcid":false,"given":"Hiroko","family":"Miyadera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsushi","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,20]]},"reference":[{"key":"BFjhg2015100_CR1","doi-asserted-by":"publisher","first-page":"D423","DOI":"10.1093\/nar\/gku1161","volume":"43","author":"J Robinson","year":"2015","unstructured":"Robinson, J., Halliwell, J. A., Hayhurst, J. D., Flicek, P., Parham, P. & Marsh, Steven, G. E. The IPD and IMGT\/HLA database: allele variant databases. Nucleic Acids Res. 43, D423\u2013D431 (2015).","journal-title":"Nucleic Acids Res."},{"key":"BFjhg2015100_CR2","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/S0140-6736(74)90021-X","volume":"1","author":"HO McDevitt","year":"1974","unstructured":"McDevitt, H. O. & Bodmer, W. F. HL-A, immune-response genes, and disease. Lancet 1, 1269\u20131275 (1974).","journal-title":"Lancet"},{"key":"BFjhg2015100_CR3","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1002\/art.1780301102","volume":"30","author":"PK Gregersen","year":"1987","unstructured":"Gregersen, P. K., Silver, J. & Winchester, R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 30, 1205\u20131213 (1987).","journal-title":"Arthritis Rheum."},{"key":"BFjhg2015100_CR4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/gene.2011.60","volume":"13","author":"SL Mackie","year":"2012","unstructured":"Mackie, S. L., Taylor, J. C., Martin, S. G ., Consortium, Y., Consortium, U. Wordsworth, P. et al. A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1: stratification by autoantibody status in a large UK population. Genes Immun. 13, 120\u2013128 (2012).","journal-title":"Genes Immun."},{"key":"BFjhg2015100_CR5","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1002\/art.24752","volume":"60","author":"AW Morgan","year":"2009","unstructured":"Morgan, A. W., Thomson, W., Martin, S. G . Yorkshire Early Arthritis Register, C., Carter, A. M ., Consortium, U. K. R. A. G. et al. Reevaluation of the interaction between HLA-DRB1 shared epitope alleles, PTPN22, and smoking in determining susceptibility to autoantibody-positive and autoantibody-negative rheumatoid arthritis in a large UK Caucasian population. Arthritis Rheum. 60, 2565\u20132576 (2009).","journal-title":"Arthritis Rheum."},{"key":"BFjhg2015100_CR6","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.1076","volume":"44","author":"S Raychaudhuri","year":"2012","unstructured":"Raychaudhuri, S., Sandor, C., Stahl, E. A., Freudenberg, J., Lee, H. S., Jia, X. et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat. Genet. 44, 291\u2013296 (2012).","journal-title":"Nat. Genet."},{"key":"BFjhg2015100_CR7","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/art.27366","volume":"62","author":"D van der Woude","year":"2010","unstructured":"van der Woude, D., Lie, B. A., Lundstrom, E., Balsa, A., Feitsma, A. L., Houwing-Duistermaat, J. J. et al. Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLA-DRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in four European populations. Arthritis Rheum. 62, 1236\u20131245 (2010).","journal-title":"Arthritis Rheum."},{"key":"BFjhg2015100_CR8","doi-asserted-by":"publisher","first-page":"973","DOI":"10.3346\/jkms.2007.22.6.973","volume":"22","author":"KR Jun","year":"2007","unstructured":"Jun, K. R., Choi, S. E., Cha, C. H., Oh, H. B., Heo, Y. S., Ahn, H. Y. et al. Meta-analysis of the association between HLA-DRB1 allele and rheumatoid arthritis susceptibility in Asian populations. J. Korean Med. Sci. 22, 973\u2013980 (2007).","journal-title":"J. Korean Med. Sci."},{"key":"BFjhg2015100_CR9","doi-asserted-by":"publisher","first-page":"3468","DOI":"10.1002\/art.20608","volume":"50","author":"HS Lee","year":"2004","unstructured":"Lee, H. S., Lee, K. W., Song, G. G., Kim, H. A., Kim, S. Y. & Bae, S. C. Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and *0901. Arthritis Rheum. 50, 3468\u20133475 (2004).","journal-title":"Arthritis Rheum."},{"key":"BFjhg2015100_CR10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1399-0039.2012.01872.x","volume":"80","author":"S Mitsunaga","year":"2012","unstructured":"Mitsunaga, S., Suzuki, Y., Kuwana, M., Sato, S., Kaneko, Y., Homma, Y. et al. Associations between six classical HLA loci and rheumatoid arthritis: a comprehensive analysis. Tissue Antigens 80, 16\u201325 (2012).","journal-title":"Tissue Antigens"},{"key":"BFjhg2015100_CR11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/jhg.2015.36","volume":"60","author":"H Furukawa","year":"2015","unstructured":"Furukawa, H., Oka, S., Shimada, K., Hashimoto, A. & Tohma, S. Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis. J. Hum. Genet. 60, 691\u2013696 (2015).","journal-title":"J. Hum. Genet."},{"key":"BFjhg2015100_CR12","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/S0198-8859(00)00185-3","volume":"61","author":"E Zanelli","year":"2000","unstructured":"Zanelli, E., Breedveld, F. C. & de Vries, R. R. HLA class II association with rheumatoid arthritis: facts and interpretations. Hum. Immunol. 61, 1254\u20131261 (2000).","journal-title":"Hum. Immunol."},{"key":"BFjhg2015100_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S0198-8859(01)00226-9","volume":"62","author":"C Seidl","year":"2001","unstructured":"Seidl, C., Korbitzer, J., Badenhoop, K., Seifried, E., Hoelzer, D., Zanelli, E. et al. Protection against severe disease is conferred by DERAA-bearing HLA-DRB1 alleles among HLA-DQ3 and HLA-DQ5 positive rheumatoid arthritis patients. Hum. Immunol. 62, 523\u2013529 (2001).","journal-title":"Hum. Immunol."},{"key":"BFjhg2015100_CR14","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1084\/jem.181.5.1847","volume":"181","author":"J Hammer","year":"1995","unstructured":"Hammer, J., Gallazzi, F., Bono, E., Karr, R. W., Guenot, J., Valsasnini, P. et al. Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid arthritis association. J. Exp. Med. 181, 1847\u20131855 (1995).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015100_CR15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/BF02786328","volume":"16","author":"I Auger","year":"1997","unstructured":"Auger, I., Toussirot, E. & Roudier, J. Molecular mechanisms involved in the association of HLA-DR4 and rheumatoid arthritis. Immunol. Res. 16, 121\u2013126 (1997).","journal-title":"Immunol. Res."},{"key":"BFjhg2015100_CR16","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/ar91","volume":"2","author":"J Roudier","year":"2000","unstructured":"Roudier, J. Association of MHC and rheumatoid arthritis. Association of RA with HLA-DR4: the role of repertoire selection. Arthritis Res. 2, 217\u2013220 (2000).","journal-title":"Arthritis Res."},{"key":"BFjhg2015100_CR17","doi-asserted-by":"publisher","first-page":"538","DOI":"10.4049\/jimmunol.171.2.538","volume":"171","author":"JA Hill","year":"2003","unstructured":"Hill, J. A., Southwood, S., Sette, A., Jevnikar, A. M., Bell, D. A. & Cairns, E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J. Immunol. 171, 538\u2013541 (2003).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR18","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1084\/jem.20131241","volume":"210","author":"SW Scally","year":"2013","unstructured":"Scally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L. et al. A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J. Exp. Med. 210, 2569\u20132582 (2013).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015100_CR19","doi-asserted-by":"publisher","first-page":"6916","DOI":"10.1093\/hmg\/ddu387","volume":"23","author":"Y Okada","year":"2014","unstructured":"Okada, Y., Kim, K., Han, B., Pillai, N. E., Ong, R. T., Saw, W. Y. et al. Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations. Hum. Mol. Genet. 23, 6916\u20136926 (2014).","journal-title":"Hum. Mol. Genet."},{"key":"BFjhg2015100_CR20","doi-asserted-by":"publisher","first-page":"6681","DOI":"10.1038\/ncomms7681","volume":"6","author":"J van Heemst","year":"2015","unstructured":"van Heemst, J., Jansen, D. T., Polydorides, S., Moustakas, A. K., Bax, M., Feitsma, A. L. et al. Crossreactivity to vinculin and microbes provides a molecular basis for HLA-based protection against rheumatoid arthritis. Nat. Commun. 6, 6681 (2015).","journal-title":"Nat. Commun."},{"key":"BFjhg2015100_CR21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1046\/j.1365-2834.2003.00373.x","volume":"11","author":"Y Ohnishi","year":"2003","unstructured":"Ohnishi, Y., Tsutsumi, A., Sakamaki, T. & Sumida, T. T cell epitopes of type II collagen in HLA-DRB1*0101 or DRB1*0405-positive Japanese patients with rheumatoid arthritis. Int. J. Mol. Med. 11, 331\u2013335 (2003).","journal-title":"Int. J. Mol. Med."},{"key":"BFjhg2015100_CR22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s002510050461","volume":"49","author":"BY Diab","year":"1999","unstructured":"Diab, B. Y., Lambert, N. C., L'Faqihi, F. E., Loubet-Lescoulie, P., de Preval, C. & Coppin, H. Human collagen II peptide 256-271 preferentially binds to HLA-DR molecules associated with susceptibility to rheumatoid arthritis. Immunogenetics 49, 36\u201344 (1999).","journal-title":"Immunogenetics"},{"key":"BFjhg2015100_CR23","doi-asserted-by":"publisher","first-page":"253","DOI":"10.4049\/jimmunol.168.1.253","volume":"168","author":"EF Rosloniec","year":"2002","unstructured":"Rosloniec, E. F., Whittington, K. B., Zaller, D. M. & Kang, A. H. HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) use the same anchor residues for binding an immunodominant peptide derived from human type II collagen. J. Immunol. 168, 253\u2013259 (2002).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR24","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1093\/intimm\/8.5.757","volume":"8","author":"S Matsushita","year":"1996","unstructured":"Matsushita, S., Nishi, T., Oiso, M., Yamaoka, K., Yone, K., Kanai, T. et al. HLA-DQ-binding peptide motifs. 1. Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthritis-susceptible and non-susceptible haplotypes. Int. Immunol. 8, 757\u2013764 (1996).","journal-title":"Int. Immunol."},{"key":"BFjhg2015100_CR25","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1002\/eji.200939482","volume":"40","author":"S Trembleau","year":"2010","unstructured":"Trembleau, S., Hoffmann, M., Meyer, B., Nell, V., Radner, H., Zauner, W. et al. Immunodominant T-cell epitopes of hnRNP-A2 associated with disease activity in patients with rheumatoid arthritis. Eur. J. Immunol. 40, 1795\u20131808 (2010).","journal-title":"Eur. J. Immunol."},{"key":"BFjhg2015100_CR26","doi-asserted-by":"publisher","first-page":"7157","DOI":"10.4049\/jimmunol.167.12.7157","volume":"167","author":"NS Patil","year":"2001","unstructured":"Patil, N. S., Pashine, A., Belmares, M. P., Liu, W., Kaneshiro, B., Rabinowitz, J. et al. Rheumatoid arthritis (RA)-associated HLA-DR alleles form less stable complexes with class II-associated invariant chain peptide than non-RA-associated HLA-DR alleles. J. Immunol. 167, 7157\u20137168 (2001).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR27","doi-asserted-by":"publisher","first-page":"3787","DOI":"10.1073\/pnas.1401105111","volume":"111","author":"H Jin","year":"2014","unstructured":"Jin, H., Arase, N., Hirayasu, K., Kohyama, M., Suenaga, T., Saito, F. et al. Autoantibodies to IgG\/HLA class II complexes are associated with rheumatoid arthritis susceptibility. Proc. Natl Acad. Sci. USA 111, 3787\u20133792 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR28","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/sj.gene.6364106","volume":"5","author":"BPC Koeleman","year":"2004","unstructured":"Koeleman, B. P. C., Lie, B. A., Undlien, D. E., Dudbridge, F., Thorsby, E., de Vries, R. R. P. et al. Genotype effects and epistasis in type 1 diabetes and HLA-DQ trans dimer associations with disease. Genes Immun. 5, 381\u2013388 (2004).","journal-title":"Genes Immun."},{"key":"BFjhg2015100_CR29","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1111\/j.1399-0039.2007.00867.x","volume":"70","author":"G Thomson","year":"2007","unstructured":"Thomson, G., Valdes, A. M., Noble, J. A., Kockum, I., Grote, M. N., Najman, J. et al. Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis. Tissue Antigens 70, 110\u2013127 (2007).","journal-title":"Tissue Antigens"},{"key":"BFjhg2015100_CR30","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.2337\/db07-1331","volume":"57","author":"H Erlich","year":"2008","unstructured":"Erlich, H., Valdes, A. M., Noble, J., Carlson, J. A., Varney, M., Concannon, P. et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 57, 1084\u20131092 (2008).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR31","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1007\/s00125-009-1539-9","volume":"52","author":"Y Kawabata","year":"2009","unstructured":"Kawabata, Y., Ikegami, H., Awata, T., Imagawa, A., Maruyama, T., Kawasaki, E. et al. Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset. Diabetologia 52, 2513\u20132521 (2009).","journal-title":"Diabetologia"},{"key":"BFjhg2015100_CR32","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/329599a0","volume":"329","author":"J Todd","year":"1987","unstructured":"Todd, J., Bell, J. & McDevitt, H. HLA-DQ\u03b2 gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329, 599\u2013604 (1987).","journal-title":"Nature"},{"key":"BFjhg2015100_CR33","doi-asserted-by":"publisher","first-page":"8111","DOI":"10.1073\/pnas.85.21.8111","volume":"85","author":"PA Morel","year":"1988","unstructured":"Morel, P. A., Dorman, J. S., Todd, J. A., McDevitt, H. O. & Trucco, M. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study. Proc. Natl Acad. Sci. USA 85, 8111\u20138115 (1988).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR34","doi-asserted-by":"publisher","first-page":"3292","DOI":"10.2337\/db13-0094","volume":"62","author":"JA Noble","year":"2013","unstructured":"Noble, J. A., Johnson, J., Lane, J. A. & Valdes, A. M. HLA class II genotyping of African American type 1 diabetic patients reveals associations unique to African haplotypes. Diabetes 62, 3292\u20133299 (2013).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR35","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1172\/JCI112903","volume":"79","author":"S Baekkeskov","year":"1987","unstructured":"Baekkeskov, S., Landin, M., Kristensen, J. K., Srikanta, S., Bruining, G. J., Mandrup-Poulsen, T. et al. Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J. Clin. Invest. 79, 926\u2013934 (1987).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015100_CR36","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1172\/JCI118188","volume":"96","author":"MA Payton","year":"1995","unstructured":"Payton, M. A., Hawkes, C. J. & Christie, M. R. Relationship of the 37,000- and 40,000-M(r) tryptic fragments of islet antigens in insulin-dependent diabetes to the protein tyrosine phosphatase-like molecule IA-2 (ICA512). J. Clin. Invest. 96, 1506\u20131511 (1995).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015100_CR37","doi-asserted-by":"publisher","first-page":"17040","DOI":"10.1073\/pnas.0705894104","volume":"104","author":"JM Wenzlau","year":"2007","unstructured":"Wenzlau, J. M., Juhl, K., Yu, L., Moua, O., Sarkar, S. A., Gottlieb, P. et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc. Natl Acad. Sci. USA 104, 17040\u201317045 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR38","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.2337\/diabetes.48.10.1937","volume":"48","author":"E Harfouch-Hammoud","year":"1999","unstructured":"Harfouch-Hammoud, E., Walk, T., Otto, H., Jung, G., Bach, J., van Endert, P. et al. Identification of peptides from autoantigens GAD65 and IA-2 that bind to HLA class II molecules predisposing to or protecting from type 1 diabetes. Diabetes 48, 1937\u20131947 (1999).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR39","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.2337\/diabetes.47.10.1594","volume":"47","author":"A Geluk","year":"1998","unstructured":"Geluk, A., van Meijgaarden, K. E., Schloot, N. C., Drijfhout, J. W., Ottenhoff, T. H. & Roep, B. O. HLA-DR binding analysis of peptides from islet antigens in IDDM. Diabetes 47, 1594\u20131601 (1998).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR40","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.4049\/jimmunol.160.5.2365","volume":"160","author":"RA Ettinger","year":"1998","unstructured":"Ettinger, R. A. & Kwok, W. W. A peptide binding motif for HLA-DQA1*0102\/DQB1*0602, the class II MHC molecule associated with dominant protection in insulin-dependent diabetes mellitus. J. Immunol. 160, 2365\u20132373 (1998).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR41","doi-asserted-by":"publisher","first-page":"5098","DOI":"10.4049\/jimmunol.169.9.5098","volume":"169","author":"J Sidney","year":"2002","unstructured":"Sidney, J., del Guercio, M.-F., Southwood, S. & Sette, A. The HLA molecules DQA1*0501\/B1*0201 and DQA1*0301\/B1*0302 share an extensive overlap in peptide binding specificity. J. Immunol. 169, 5098\u20135108 (2002).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR42","doi-asserted-by":"publisher","first-page":"4189","DOI":"10.4049\/jimmunol.1001006","volume":"185","author":"J Sidney","year":"2010","unstructured":"Sidney, J., Steen, A., Moore, C., Ngo, S., Chung, J., Peters, B. et al. Divergent motifs but overlapping binding repertoires of six HLA-DQ molecules frequently expressed in the worldwide human population. J. Immunol. 185, 4189\u20134198 (2010).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR43","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1744-313X.2008.00823.x","volume":"36","author":"AC Britten","year":"2009","unstructured":"Britten, A. C., Mijovic, C. H., Barnett, A. H. & Kelly, M. A. Differential expression of HLA-DQ alleles in peripheral blood mononuclear cells: alleles associated with susceptibility to and protection from autoimmune type 1 diabetes. Int. J. Immunogenet. 36, 47\u201357 (2009).","journal-title":"Int. J. Immunogenet."},{"key":"BFjhg2015100_CR44","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1017\/erm.2012.9","volume":"14","author":"R Busch","year":"2012","unstructured":"Busch, R., De Riva, A., Hadjinicolaou, A. V., Jiang, W., Hou, T. & Mellins, E. D. On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes. Expert Rev. Mol. Med. 14, e15 (2012).","journal-title":"Expert Rev. Mol. Med."},{"key":"BFjhg2015100_CR45","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/j.0105-2896.2005.00306.x","volume":"207","author":"R Busch","year":"2005","unstructured":"Busch, R., Rinderknecht, C. H., Roh, S., Lee, A. W., Harding, J. J., Burster, T. et al. Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression. Immunol. Rev. 207, 242\u2013260 (2005).","journal-title":"Immunol. Rev."},{"key":"BFjhg2015100_CR46","doi-asserted-by":"publisher","first-page":"262","DOI":"10.3389\/fimmu.2013.00262","volume":"4","author":"Z Zhou","year":"2013","unstructured":"Zhou, Z. & Jensen, P. E. Structural characteristics of HLA-DQ that may impact DM editing and susceptibility to Type-1 diabetes. Front. Immunol. 4, 262 (2013).","journal-title":"Front. Immunol."},{"key":"BFjhg2015100_CR47","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1126\/science.288.5465.505","volume":"288","author":"AL Corper","year":"2000","unstructured":"Corper, A. L., Stratmann, T., Apostolopoulos, V., Scott, C. A., Garcia, K. C., Kang, A. S. et al. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes. Science 288, 505\u2013511 (2000).","journal-title":"Science"},{"key":"BFjhg2015100_CR48","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/S1074-7613(00)80220-4","volume":"12","author":"RR Latek","year":"2000","unstructured":"Latek, R. R., Suri, A., Petzold, S. J., Nelson, C. A., Kanagawa, O., Unanue, E. R. et al. Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice. Immunity 12, 699\u2013710 (2000).","journal-title":"Immunity"},{"key":"BFjhg2015100_CR49","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/88694","volume":"2","author":"KH Lee","year":"2001","unstructured":"Lee, K. H., Wucherpfennig, K. W. & Wiley, D. C. Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes. Nat. Immunol. 2, 501\u2013507 (2001).","journal-title":"Nat. Immunol."},{"key":"BFjhg2015100_CR50","doi-asserted-by":"publisher","first-page":"6051","DOI":"10.4049\/jimmunol.178.10.6051","volume":"178","author":"MG Levisetti","year":"2007","unstructured":"Levisetti, M. G., Suri, A., Petzold, S. J. & Unanue, E. R. The insulin-specific T cells of nonobese diabetic mice recognize a weak MHC-binding segment in more than one form. J. Immunol. 178, 6051\u20136057 (2007).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR51","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.2337\/db08-0068","volume":"57","author":"MG Levisetti","year":"2008","unstructured":"Levisetti, M. G., Lewis, D. M., Suri, A. & Unanue, E. R. Weak proinsulin peptide-major histocompatibility complexes are targeted in autoimmune diabetes in mice. Diabetes 57, 1852\u20131860 (2008).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR52","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/ni.1844","volume":"11","author":"BD Stadinski","year":"2010","unstructured":"Stadinski, B. D., Delong, T., Reisdorph, N., Reisdorph, R., Powell, R. L., Armstrong, M. et al. Chromogranin A is an autoantigen in type 1 diabetes. Nat. Immunol. 11, 225\u2013231 (2010).","journal-title":"Nat. Immunol."},{"key":"BFjhg2015100_CR53","doi-asserted-by":"publisher","first-page":"10978","DOI":"10.1073\/pnas.1006545107","volume":"107","author":"BD Stadinski","year":"2010","unstructured":"Stadinski, B. D., Zhang, L., Crawford, F., Marrack, P., Eisenbarth, G. S. & Kappler, J. W. Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. Proc. Natl Acad. Sci. USA 107, 10978\u201310983 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR54","doi-asserted-by":"publisher","first-page":"16729","DOI":"10.1073\/pnas.1113954108","volume":"108","author":"F Crawford","year":"2011","unstructured":"Crawford, F., Stadinski, B., Jin, N., Michels, A., Nakayama, M., Pratt, P. et al. Specificity and detection of insulin-reactive CD4+ T cells in type 1 diabetes in the nonobese diabetic (NOD) mouse. Proc. Natl Acad. Sci. USA 108, 16729\u201316734 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR55","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1093\/intimm\/10.12.1765","volume":"10","author":"RJ Boyton","year":"1998","unstructured":"Boyton, R. J., Lohmann, T., Londei, M., Kalbacher, H., Halder, T., Frater, A. J. et al. Glutamic acid decarboxylase T lymphocyte responses associated with susceptibility or resistance to type I diabetes: analysis in disease discordant human twins, non-obese diabetic mice and HLA-DQ transgenic mice. Int. Immun. 10, 1765\u20131776 (1998).","journal-title":"Int. Immun."},{"key":"BFjhg2015100_CR56","doi-asserted-by":"publisher","first-page":"14840","DOI":"10.1073\/pnas.1416864111","volume":"111","author":"J Yang","year":"2014","unstructured":"Yang, J., Chow, I.-T., Sosinowski, T., Torres-Chinn, N., Greenbaum, C. J., James, E. A. et al. Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes. Proc. Natl Acad. Sci. USA 111, 14840\u201314845 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR57","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.2337\/db08-0530","volume":"57","author":"EA James","year":"2008","unstructured":"James, E. A. & Kwok, W. W. Low-affinity major histocompatibility complex-binding peptides in type 1 diabetes. Diabetes 57, 1788\u20131789 (2008).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR58","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.4049\/jimmunol.161.11.6439","volume":"161","author":"RA Ettinger","year":"1998","unstructured":"Ettinger, R. A., Liu, A. W., Nepom, G. T. & Kwok, W. W. Exceptional stability of the HLA-DQA1*0102\/DQB1*0602 \u03b1\u03b2 protein dimer, the class II MHC molecule associated with protection from insulin-dependent diabetes mellitus. J. Immunol. 161, 6439\u20136445 (1998).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR59","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1172\/JCI74961","volume":"125","author":"H Miyadera","year":"2015","unstructured":"Miyadera, H., Ohashi, J., Lernmark, A., Kitamura, T. & Tokunaga, K. Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA. J. Clin. Invest. 125, 275\u2013291 (2015).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015100_CR60","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.2337\/diab.39.10.1153","volume":"39","author":"GT Nepom","year":"1990","unstructured":"Nepom, G. T. A unified hypothesis for the complex genetics of HLA associations with IDDM. Diabetes 39, 1153\u20131157 (1990).","journal-title":"Diabetes"},{"key":"BFjhg2015100_CR61","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1084\/jem.178.5.1675","volume":"178","author":"H Deng","year":"1993","unstructured":"Deng, H., Apple, R., Clare-Salzler, M., Trembleau, S., Mathis, D., Adorini, L. et al. Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease. J. Exp. Med. 178, 1675\u20131680 (1993).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015100_CR62","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/gene.2011.24","volume":"12","author":"P Eerligh","year":"2011","unstructured":"Eerligh, P., van Lummel, M., Zaldumbide, A., Moustakas, A. K., Duinkerken, G., Bondinas, G. et al. Functional consequences of HLA-DQ8 homozygosity versus heterozygosity for islet autoimmunity in type 1 diabetes. Genes Immun. 12, 415\u2013427 (2011).","journal-title":"Genes Immun."},{"key":"BFjhg2015100_CR63","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/0140-6736(92)90080-M","volume":"339","author":"Y Uchigata","year":"1992","unstructured":"Uchigata, Y., Kuwata, S., Tokunaga, K., Eguchi, Y., Takayama-Hasumi, S., Miyamoto, M. et al. Strong association of insulin autoimmune syndrome with HLA-DR4. Lancet 339, 393\u2013394 (1992).","journal-title":"Lancet"},{"key":"BFjhg2015100_CR64","doi-asserted-by":"crossref","first-page":"5770","DOI":"10.4049\/jimmunol.151.10.5770","volume":"151","author":"Y Ito","year":"1993","unstructured":"Ito, Y., Nieda, M., Uchigata, Y., Nishimura, M., Tokunaga, K., Kuwata, S. et al. Recognition of human insulin in the context of HLA-DRB1*0406 products by T cells of insulin autoimmune syndrome patients and healthy donors. J. Immunol. 151, 5770\u20135776 (1993).","journal-title":"J. Immunol."},{"key":"BFjhg2015100_CR65","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1093\/intimm\/4.7.773","volume":"4","author":"M Wall","year":"1992","unstructured":"Wall, M., Southwood, S., Sidney, J., Oseroff, C., del Guericio, M.-F., Lamont, A. G. et al. High affinity for class II molecules as a necessary but not sufficient characteristic of encephalitogenic determinants. Int. Immunol. 4, 773\u2013777 (1992).","journal-title":"Int. Immunol."},{"key":"BFjhg2015100_CR66","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1172\/JCI116242","volume":"91","author":"A Valli","year":"1993","unstructured":"Valli, A., Sette, A., Kappos, L., Oseroff, C., Sidney, J., Miescher, G. et al. Binding of myelin basic protein peptides to human histocompatibility leukocyte antigen class II molecules and their recognition by T cells from multiple sclerosis patients. J. Clin. Invest. 91, 616\u2013628 (1993).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015100_CR67","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1172\/JCI119539","volume":"100","author":"PA Muraro","year":"1997","unstructured":"Muraro, P. A., Vergelli, M., Kalbus, M., Banks, D. E., Nagle, J. W., Tranquill, L. R. et al. Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire. J. Clin. Invest. 100, 339\u2013349 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFjhg2015100_CR68","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/j.1399-0039.2011.01634.x","volume":"77","author":"C Weinstock","year":"2011","unstructured":"Weinstock, C., Matheis, N., Barkia, S., Haager, M. C., Janson, A., Markovic, A. et al. Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes. Tissue Antigens 77, 317\u2013324 (2011).","journal-title":"Tissue Antigens"},{"key":"BFjhg2015100_CR69","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1084\/jem.169.1.345","volume":"169","author":"LM Sollid","year":"1989","unstructured":"Sollid, L. M., Markussen, G., Ek, J., Gjerde, H., Vartdal, F. & Thorsby, E. Evidence for a primary association of celiac disease to a particular HLA-DQ \u03b1\/\u03b2 heterodimer. J. Exp. Med. 169, 345\u2013350 (1989).","journal-title":"J. Exp. Med."},{"key":"BFjhg2015100_CR70","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/0198-8859(92)90104-U","volume":"35","author":"A Spurkland","year":"1992","unstructured":"Spurkland, A., Sollid, L. M., Polanco, I., Vartdal, F. & Thorsby, E. HLA-DR and -DQ genotypes of celiac disease patients serologically typed to be non-DR3 or non-DR5\/7. Hum. Immunol. 35, 188\u2013192 (1992).","journal-title":"Hum. Immunol."},{"key":"BFjhg2015100_CR71","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1007\/s10157-012-0691-6","volume":"17","author":"N Tsuchiya","year":"2013","unstructured":"Tsuchiya, N. Genetics of ANCA-associated vasculitis in Japan: a role for HLA-DRB1*09:01 haplotype. Clin. Exp. Nephrol. 17, 628\u2013630 (2013).","journal-title":"Clin. Exp. Nephrol."},{"key":"BFjhg2015100_CR72","first-page":"253","volume":"64","author":"K Hashimoto","year":"2005","unstructured":"Hashimoto, K., Maruyama, H., Nishiyama, M., Asaba, K., Ikeda, Y., Takao, T. et al. Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population. Horm. Res. 64, 253\u2013260 (2005).","journal-title":"Horm. Res."},{"key":"BFjhg2015100_CR73","doi-asserted-by":"publisher","first-page":"18680","DOI":"10.1073\/pnas.0909307106","volume":"106","author":"JD Rioux","year":"2009","unstructured":"Rioux, J. D., Goyette, P., Vyse, T. J., Hammarstrom, L., Fernando, M. M., Green, T. et al. Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases. Proc. Natl Acad. Sci. USA 106, 18680\u201318685 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFjhg2015100_CR74","doi-asserted-by":"publisher","first-page":"e1002476","DOI":"10.1371\/journal.pgen.1002476","volume":"8","author":"RC Ferreira","year":"2012","unstructured":"Ferreira, R. C., Pan-Hammarstr\u00f6m, Q., Graham, R. R., Font\u00e1n, G., Lee, A. T., Ortmann, W. et al. High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency. PLoS Genet. 8, e1002476 (2012).","journal-title":"PLoS Genet."},{"key":"BFjhg2015100_CR75","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/S1074-7613(00)80369-6","volume":"7","author":"A Dessen","year":"1997","unstructured":"Dessen, A., Lawrence, C. M., Cupo, S., Zaller, D. M. & Wiley, D. C. X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II. Immunity 7, 473\u2013481 (1997).","journal-title":"Immunity"},{"issue":"Suppl 1","key":"BFjhg2015100_CR76","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1111\/j.1399-0039.2006.00772.x","volume":"69","author":"A Steenkiste","year":"2007","unstructured":"Steenkiste, A., Valdes, A. M., Feolo, M., Hoffman, D., Concannon, P., Noble, J. et al. 14th International HLA and Immunogenetics Workshop: report on the HLA component of type 1 diabetes. Tissue Antigens 69 (Suppl 1), 214\u2013225 (2007).","journal-title":"Tissue Antigens"},{"key":"BFjhg2015100_CR77","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1073\/pnas.0308458100","volume":"101","author":"C Siebold","year":"2004","unstructured":"Siebold, C., Hansen, B. E., Wyer, J. R., Harlos, K., Esnouf, R. E., Svejgaard, A. et al. Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy. Proc. Natl Acad. Sci. USA 101, 1999\u20132004 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/jhg2015100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg2015100","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/jhg2015100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T08:25:57Z","timestamp":1691915157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/jhg2015100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,20]]},"references-count":77,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["BFjhg2015100"],"URL":"https:\/\/doi.org\/10.1038\/jhg.2015.100","relation":{},"ISSN":["1434-5161","1435-232X"],"issn-type":[{"value":"1434-5161","type":"print"},{"value":"1435-232X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,20]]},"assertion":[{"value":"11 May 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}