{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:24:04Z","timestamp":1793507044783,"version":"4.5.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"13","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12,14]]},"abstract":"<jats:p>Psoriasis vulgaris is a common T cell\u2013mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8+ T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02\u2013restricted psoriatic T cell response. We found that a V\u03b13S1\/V\u03b213S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8+ T cell clone of an HLA-C*06:02\u2013positive psoriasis patient specifically recognizes HLA-C*06:02\u2013positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02\u2013presented melanocytic autoantigen of the V\u03b13S1\/V\u03b213S1 TCR. Consistent with the V\u03b13S1\/V\u03b213S1-TCR reactivity, we observed numerous CD8+ T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8+ T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8+ T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway.<\/jats:p>","DOI":"10.1084\/jem.20151093","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T22:38:22Z","timestamp":1448923102000},"page":"2203-2212","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":338,"title":["Melanocyte antigen triggers autoimmunity in human psoriasis"],"prefix":"10.1084","volume":"212","author":[{"given":"Akiko","family":"Arakawa","sequence":"first","affiliation":[{"name":"Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Siewert","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, Ludwig-Maximilian-University, D-82152 Planegg-Martinsried, Germany 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