{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:30:38Z","timestamp":1793824238798,"version":"4.6.1"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council UK","doi-asserted-by":"crossref","award":["BB\/H001085\/1"],"award-info":[{"award-number":["BB\/H001085\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220295\/Z\/20\/Z"],"award-info":[{"award-number":["220295\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:p>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells destroy insulin-producing pancreatic \u03b2 cells in type 1 diabetes through HLA class I\u2013restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele\n                    <jats:italic>HLA A*24:02<\/jats:italic>\n                    . Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02\u2013peptide\u2013TCR structure by crystal seeding. TCR binding to the PPI epitope was strongly focused on peptide residues Arg4 and Leu5, with more flexibility at other positions, allowing the TCR to strongly engage many peptides derived from pathogenic bacteria. We confirmed an epitope from\n                    <jats:italic>Klebsiella<\/jats:italic>\n                    that was recognized by PPI-reactive T cells from 3 of 3\n                    <jats:italic>\n                      HLA A*24:02\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    patients. Remarkably, the same epitope selected T cells from 7 of 8 HLA A*24\n                    <jats:sup>+<\/jats:sup>\n                    healthy donors that cross-reacted with PPI, leading to recognition and killing of\n                    <jats:italic>\n                      HLA A*24:02\n                      <jats:sup>+<\/jats:sup>\n                    <\/jats:italic>\n                    cells expressing PPI. These data provide a mechanism by which molecular mimicry between pathogen and self-antigens could have resulted in the breaking of self-tolerance to initiate disease.\n                  <\/jats:p>","DOI":"10.1172\/jci164535","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T14:00:41Z","timestamp":1726495241000},"source":"Crossref","is-referenced-by-count":15,"title":["HLA A*24:02\u2013restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-9108","authenticated-orcid":true,"given":"Garry","family":"Dolton","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bulek","sequence":"additional","affiliation":[{"name":"Division of Infection and 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