{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:05:41Z","timestamp":1784621141782,"version":"3.55.0"},"reference-count":46,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Leonardo","award":["None"],"award-info":[{"award-number":["None"]}]},{"DOI":"10.13039\/501100013850","name":"Helmut Horten Foundation","doi-asserted-by":"crossref","award":["None"],"award-info":[{"award-number":["None"]}],"id":[{"id":"10.13039\/501100013850","id-type":"DOI","asserted-by":"crossref"}]},{"name":"As already specified below","award":["As already specified below"],"award-info":[{"award-number":["As already specified below"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,16]]},"abstract":"<jats:p>\n                    Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease characterized by the presence of autoantibodies, including those targeting O-phosphoseryl-tRNA:selenocysteine-tRNA synthase (SepSecS), also known as soluble liver antigen (SLA). Anti-SepSecS antibodies have been associated with a more severe phenotype, suggesting a key role for the SepSecS autoantigen in AIH. To analyze the immune response to SepSecS in patients with AIH at the clonal level, we combined sensitive high-throughput screening assays with the isolation of monoclonal antibodies (mAbs) and T cell clones. The anti-SepSecS mAbs isolated were primarily IgG1, affinity-matured compared with their germline versions, and recognized at least 3 nonoverlapping epitopes. SepSecS-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell clones were found in patients with AIH who were anti-SLA-positive and anti-SLA-negative,and, to a lesser extent, in patients with non-AIH liver diseases and in healthy individuals. SepSecS-specific T cell clones from patients with AIH produced IFN-\u03b3, IL-4, and IL-10, targeted multiple SepSecS epitopes, and, in one patient, were clonally expanded in both blood and liver biopsy. Finally, SepSecS-specific B cell clones, but not those of unrelated specificities, were able to present soluble SepSecS to specific T cells. Collectively, our study provides the first detailed analysis of B and T cell repertoires targeting SepSecS in patients with AIH, offering a rationale for improved targeted therapies.\n                  <\/jats:p>","DOI":"10.1172\/jci183776","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:44Z","timestamp":1736949644000},"source":"Crossref","is-referenced-by-count":19,"title":["Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis"],"prefix":"10.1172","volume":"135","author":[{"given":"Michael","family":"Kramer","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine (IRB), Bellinzona, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Mele","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB), Bellinzona, 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