{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:42:04Z","timestamp":1775043724974,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endocrine epithelial cells, targets of the autoimmune response in thyroid and other organ-specific autoimmune diseases, express HLA class II (HLA-II) molecules that are presumably involved in the maintenance and regulation of the in situ autoimmune response. HLA-II molecules thus expressed by thyroid cells have the \u201ccompact\u201d conformation and are therefore expected to stably bind autologous peptides. Using a new approach to study in situ T cell responses without the characterization of self-reactive T cells and their specificity, we have identified natural HLA-DR-associated peptides in autoimmune organs that will allow finding peptide-specific T cells in situ. This study reports a first analysis of HLA-DR natural ligands from ex vivo Graves\u2019 disease-affected thyroid tissue. Using mass spectrometry, we identified 162 autologous peptides from HLA-DR-expressing cells, including thyroid follicular cells, with some corresponding to predominant molecules of the thyroid colloid. Most interestingly, eight of the peptides were derived from a major autoantigen, thyroglobulin. In vitro binding identified HLA-DR3 as the allele to which one of these peptides likely associates in vivo. Computer modeling and bioinformatics analysis suggested other HLA-DR alleles for binding of other thyroglobulin peptides. Our data demonstrate that although the HLA-DR-associated peptide pool in autoimmune tissue mostly belongs to abundant ubiquitous proteins, peptides from autoantigens are also associated to HLA-DR in vivo and therefore may well be involved in the maintenance and the regulation of the autoimmune response.<\/jats:p>","DOI":"10.4049\/jimmunol.181.1.795","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:04:22Z","timestamp":1397847862000},"page":"795-807","source":"Crossref","is-referenced-by-count":45,"title":["Thyroglobulin Peptides Associate In Vivo to HLA-DR in Autoimmune Thyroid Glands"],"prefix":"10.1093","volume":"181","author":[{"given":"Laia","family":"Muix\u00ed","sequence":"first","affiliation":[{"name":"Immunology Unit, Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Carrascal","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cientificas-Universitat Aut\u00f2noma de Baracelona, Proteomics Facility, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona, Consejo Superior de Investigaciones Cientificas-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I\u00f1aki","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Immunology Unit, Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Daura","sequence":"additional","affiliation":[{"name":"Catalan Institution for Research and Advanced Studies and Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merc\u00e8","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Immunology Unit, Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pilar","family":"Armengol","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology for Research and Application to Diagnosis, Blood and Tissue Bank, University Hospital Germans Trias i Pujol, Badalona, and Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona , Barcelona,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemencia","family":"Pinilla","sequence":"additional","affiliation":[{"name":"Torrey Pines Institute for Molecular Studies , San Diego, CA 92121"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn","family":"Abian","sequence":"additional","affiliation":[{"name":"Consejo Superior de Investigaciones Cientificas-Universitat Aut\u00f2noma de Baracelona, Proteomics Facility, Institut d\u2019Investigacions Biom\u00e8diques de Barcelona, Consejo Superior de Investigaciones Cientificas-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Pujol-Borrell","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology for Research and Application to Diagnosis, Blood and Tissue Bank, University Hospital Germans Trias i Pujol, Badalona, and Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona , Barcelona,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Jaraquemada","sequence":"additional","affiliation":[{"name":"Immunology Unit, Institut de Biotecnologia i Biomedicina, Universitat Aut\u00f2noma de Barcelona , Barcelona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2026012809121341800_R1","first-page":"1111","article-title":"Aberrant expression of HLA-DR antigen on thyrocytes in Graves\u2019 disease: relevance for autoimmunity","volume-title":"Lancet","year":"1983"},{"key":"2026012809121341800_R2","first-page":"247","article-title":"Control of MHC class II gene expression in autoimmune, infectious, and neoplastic diseases","volume-title":"Crit. 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