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Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors.
Wu, Daichao; Kolesnikov, Alexander; Yin, Rui; Guest, Johnathan D; Gowthaman, Ragul; Shmelev, Anton; Serdyuk, Yana; Dianov, Dmitry V; Efimov, Grigory A; Pierce, Brian G; Mariuzza, Roy A.
  • Wu D; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.
  • Kolesnikov A; Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
  • Yin R; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
  • Guest JD; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.
  • Gowthaman R; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
  • Shmelev A; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.
  • Serdyuk Y; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
  • Dianov DV; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.
  • Efimov GA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
  • Pierce BG; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.
  • Mariuzza RA; Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
Nat Commun ; 13(1): 19, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1616981
ABSTRACT
T cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide-MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / HLA-A2 Antigen / Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-021-27669-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / HLA-A2 Antigen / Epitopes, T-Lymphocyte / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Observational study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-021-27669-8