{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:34:36Z","timestamp":1785429276495,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,24]]},"group-title":"Immunology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science","award":["2024-I2M-2-001-1"],"award-info":[{"award-number":["2024-I2M-2-001-1"]}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["MR\/Y015347\/1"],"award-info":[{"award-number":["MR\/Y015347\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"crossref","award":["IMMPROVE - MR\/Y004450\/1"],"award-info":[{"award-number":["IMMPROVE - MR\/Y004450\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["311427\/Z\/24\/Z"],"award-info":[{"award-number":["311427\/Z\/24\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54 AI170791"],"award-info":[{"award-number":["U54 AI170791"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21 AI184080"],"award-info":[{"award-number":["R21 AI184080"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["101021133"],"award-info":[{"award-number":["101021133"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Public T cell receptors (TCRs) recurrently emerge across individuals in response to common pathogens, yet the structural and biophysical basis distinguishing public from private clonotypes remains incompletely defined. Here, we combine epitope mapping, single-cell TCR sequencing, and single-particle cryo-electron microscopy to dissect CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell responses to the immunodominant SARS-CoV-2 ORF3a(207\u2013215) epitope presented by HLA-A*01:01. Among responding clonotypes, we identify a shared public TCR (TCRpub) and an individual-specific private TCR (TCRpriv) that use nearly identical TRBV5-1 \u03b2 chains but distinct \u03b1 chains. Both clonotypes exhibit comparable micromolar affinity and functional avidity, yet their structures reveal different antigen-recognition modes. We determined cryo-EM structures of the TCR\n                  <jats:sub>pub<\/jats:sub>\n                  and TCR\n                  <jats:sub>priv<\/jats:sub>\n                  in complex with ORF3a\n                  <jats:sub>(207-215)<\/jats:sub>\n                  \/ HLA-A*01:01 at \u223c3 \u00c5 resolution. Despite targeting the same epitope, the two receptors engaged the peptide-MHC complex with distinct CDR-loop orientations and contact footprints: TCRpub engages the peptide through a peptide-centric AGDL CDR3\u03b2 motif and focuses interactions on the MHC \u03b12-helix, whereas TCRpriv distributes contacts across both MHC \u03b1-helices via a canonical CDR3\u03b2 configuration. These findings illustrate how near-identical \u03b2 chains can yield divergent recognition strategies to recognise the same pMHC ligand through alternative \u03b1-chain pairing. More broadly, this work establishes cryo-EM as a robust approach for resolving physiological-affinity TCR\/pMHC complexes, providing mechanistic insight into how public TCRs emerge and persist in antiviral immunity.\n                <\/jats:p>","DOI":"10.1101\/2025.11.23.690020","type":"posted-content","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T02:30:16Z","timestamp":1764037816000},"source":"Crossref","is-referenced-by-count":0,"title":["Uncovering structural determinants of peptide recognition by public and private T-cell receptors"],"prefix":"10.64898","author":[{"given":"Caner","family":"Ak\u0131l","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Hardenbrook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danning","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Antoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Bal\u0131k\u00e7\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Cioaca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunkai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-2209","authenticated-orcid":false,"given":"Alexander 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