{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:41:20Z","timestamp":1790613680567,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"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":[[2003,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The MHC determines susceptibility and resistance to type 1 diabetes in humans and nonobese diabetic (NOD) mice. To investigate how a disease-associated MHC molecule shapes the T cell repertoire in NOD mice, we generated a series of tetramers from I-Ag7\/class II-associated invariant chain peptide precursors by peptide exchange. No CD4 T cell populations could be identified for two glutamic acid decarboxylase 65 peptides, but tetramers with a peptide mimetic recognized by the BDC-2.5 and other islet-specific T cell clones labeled a distinct population in the thymus of young NOD mice. Tetramer-positive cells were identified in the immature CD4+CD8low population that arises during positive selection, and in larger numbers in the more mature CD4+CD8\u2212 population. Tetramer labeling was specific based on the use of multiple control tetramers, including one with a single amino acid analog peptide in which a critical TCR contact residue was substituted. The T cell population was already present in the thymus of 2-wk-old NOD mice before the typical onset of insulitis and was detected in B10 mice congenic for the NOD MHC locus, but not B10 control mice. These results demonstrate that a T cell population can expand in the thymus of NOD mice to levels that are at least two to three orders of magnitude higher than estimated for a given specificity in the naive T cell pool. Based on these data, we propose a model in which I-Ag7 confers susceptibility to type 1 diabetes by biasing positive selection in the thymus and later presenting peptides from islet autoantigens to such T cells in the periphery.<\/jats:p>","DOI":"10.4049\/jimmunol.171.8.4175","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T20:53:23Z","timestamp":1398027203000},"page":"4175-4186","source":"Crossref","is-referenced-by-count":44,"title":["Ex Vivo Analysis of Thymic CD4 T Cells in Nonobese Diabetic Mice with Tetramers Generated from I-Ag7\/Class II-Associated Invariant Chain Peptide Precursors"],"prefix":"10.1093","volume":"171","author":[{"given":"Mei-Huei","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Department of Pathology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufer P","family":"Seth","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Department of Pathology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai W","family":"Wucherpfennig","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA 02115"},{"name":"Department ofNeurology, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,10,15]]},"reference":[{"key":"2026020210180256700_R1","first-page":"650","volume-title":"Curr. 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