{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:33:35Z","timestamp":1791405215431,"version":"4.3.3"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:p>Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DP\u2013restricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2\u2013mimotope and HLA-DP2\u2013plexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD.<\/jats:p>","DOI":"10.1084\/jem.20122426","type":"journal-article","created":{"date-parts":[[2013,6,24]],"date-time":"2013-06-24T23:23:05Z","timestamp":1372116185000},"page":"1403-1418","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease"],"prefix":"10.1084","volume":"210","author":[{"given":"Michael T.","family":"Falta","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Colorado, Denver, Aurora, CO 80045 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemencia","family":"Pinilla","sequence":"additional","affiliation":[{"name":"Torrey 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