{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:10:00Z","timestamp":1782216600658,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dutch Arthritis Foundation","award":["2013-2-024"],"award-info":[{"award-number":["2013-2-024"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)","award":["R01-AR-059356"],"award-info":[{"award-number":["R01-AR-059356"]}]},{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)","award":["R01-AR-062991"],"award-info":[{"award-number":["R01-AR-062991"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We previously showed that mycobacterial Hsp70\u2010derived peptide B29 induced B29\u2010specific Treg cells that suppressed experimental arthritis in mice via cross\u2010recognition of their mammalian Hsp70 homologs. The aim of the current study was to characterize B29 binding and specific CD4+ T cell responses in the context of human major histocompatibility complex (MHC) molecules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Competitive binding assays were performed to examine binding of peptide B29 and its mammalian homologs to HLA molecules. The effect of B29 immunization in HLA\u2013DQ8\u2013transgenic mice with proteoglycan\u2010induced arthritis was assessed, followed by ex vivo restimulation with B29 to examine the T cell response. Human peripheral blood mononuclear cells were used to investigate the presence of B29\u2010specific T cells with immunoregulatory potential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The binding affinity of the B29 peptide was high to moderate for multiple HLA\u2013DR and HLA\u2013DQ molecules, including those highly associated with rheumatoid arthritis. This binding was considered to be functional, because B29 immunization resulted in the suppression of arthritis and T cell responses in HLA\u2013DQ8\u2013transgenic mice. In humans, we demonstrated the presence and expansion of B29\u2010specific CD4+ T cells, which were cross\u2010reactive with the mammalian homologs. Using HLA\u2013DR4+ tetramers specific for B29 or the mammalian homolog mB29b, we showed expansion of cross\u2010reactive T cells, especially the human FoxP3+ CD4+CD25+ T cell population, after in vitro stimulation with B29.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results demonstrated a conserved fine specificity and functionality of B29\u2010induced Treg cell responses in the context of the human MHC. Based on these findings, a path for translation of the experimental findings for B29 into a clinical immunomodulatory therapeutic approach is within reach.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39444","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T12:49:57Z","timestamp":1443444597000},"page":"639-647","source":"Crossref","is-referenced-by-count":22,"title":["An Arthritis\u2010Suppressive and Treg Cell\u2013Inducing CD4+ T Cell Epitope Is Functional in the Context of HLA\u2010Restricted T Cell Responses"],"prefix":"10.1002","volume":"68","author":[{"given":"Charlotte","family":"de Wolf","sequence":"first","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruurd","family":"van der Zee","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"den Braber","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Glant","sequence":"additional","affiliation":[{"name":"Rush University Medical Center Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Maill\u00e8re","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019\u00c9nergie Atomique, Institut de Biologie et de Technologies de Saclay Gif Sur Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Favry","sequence":"additional","affiliation":[{"name":"Commissariat \u00e0 l\u2019\u00c9nergie Atomique, Institut de Biologie et de Technologies de Saclay Gif Sur Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno","family":"van Lummel","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aad","family":"Hoek","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem","family":"van Eden","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Broere","sequence":"additional","affiliation":[{"name":"Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1593"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.8.3088"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.3.943"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2711"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.151274"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2010.550590"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206803109"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20285"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20180"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3177"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.313940"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2009.11.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197804202981602"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.237"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.5.1814"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364045"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.05.002"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1492"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2399"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.05.024"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501190102"}],"container-title":["Arthritis &amp; 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