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HLA-A∗02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses.

  • Nesterenko, Pavlo A
  • McLaughlin, Jami
  • Tsai, Brandon L
  • Burton Sojo, Giselle
  • Cheng, Donghui
  • Zhao, Daniel
  • Mao, Zhiyuan
  • Bangayan, Nathanael J
  • Obusan, Matthew B
  • Su, Yapeng
  • Ng, Rachel H
  • Chour, William
  • Xie, Jingyi
  • Li, Yan-Ruide
  • Lee, Derek
  • Noguchi, Miyako
  • Carmona, Camille
  • Phillips, John W
  • Kim, Jocelyn T
  • Yang, Lili
  • And 3 more
Publication Date
Dec 10, 2021
eScholarship - University of California
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Cross-reactivity and direct killing of target cells remain underexplored for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8+ T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its critical role in the virus life cycle. We perform single-cell TCRαβ sequencing in human leukocyte antigen (HLA)-A∗02:01-restricted, RdRp-specific T cells from SARS-CoV-2-unexposed individuals. Human T cells expressing these TCRαβ constructs kill target cell lines engineered to express full-length RdRp. Three TCR constructs recognize homologous epitopes from common cold coronaviruses, indicating CD8+ T cells can recognize evolutionarily diverse coronaviruses. Analysis of individual TCR clones may help define vaccine epitopes that can induce long-term immunity against SARS-CoV-2 and other coronaviruses.

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