{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:33:04Z","timestamp":1792708384895,"version":"4.5.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"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":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The molecular rules driving TCR cross-reactivity are poorly understood and, consequently, it is unclear the extent to which TCRs targeting the same Ag recognize the same off-target peptides. We determined TCR\u2013peptide\u2013HLA crystal structures and, using a single-chain peptide\u2013HLA phage library, we generated peptide specificity profiles for three newly identified human TCRs specific for the cancer testis Ag NY-ESO-1157\u2013165\u2013HLA-A2. Two TCRs engaged the same central peptide feature, although were more permissive at peripheral peptide positions and, accordingly, possessed partially overlapping peptide specificity profiles. The third TCR engaged a flipped peptide conformation, leading to the recognition of off-target peptides sharing little similarity with the cognate peptide. These data show that TCRs specific for a cognate peptide recognize discrete peptide repertoires and reconciles how an individual\u2019s limited TCR repertoire following negative selection in the thymus is able to recognize a vastly larger antigenic pool.<\/jats:p>","DOI":"10.4049\/jimmunol.1900915","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T14:55:17Z","timestamp":1582728917000},"page":"1943-1953","source":"Crossref","is-referenced-by-count":63,"title":["TCRs with Distinct Specificity Profiles Use Different Binding Modes to Engage an Identical Peptide\u2013HLA Complex"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4525-7144","authenticated-orcid":false,"given":"Charlotte H","family":"Coles","sequence":"first","affiliation":[{"name":"Immunocore, Ltd. , Abingdon, Oxfordshire OX14 4RY ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel M","family":"Mulvaney","sequence":"additional","affiliation":[{"name":"Immunocore, Ltd. , Abingdon, Oxfordshire OX14 4RY ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5653-2271","authenticated-orcid":false,"given":"Sunir","family":"Malla","sequence":"additional","affiliation":[{"name":"Immunocore, Ltd. , Abingdon, Oxfordshire OX14 4RY ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4715-4325","authenticated-orcid":false,"given":"Andrew","family":"Walker","sequence":"additional","affiliation":[{"name":"Immunocore, Ltd. , Abingdon, Oxfordshire OX14 4RY ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrine J","family":"Smith","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Medicines Research Centre , Stevenage, Hertfordshire SG1 2NY ,","place":["United 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