Title HLA-A( *)02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses.
Author 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; Heath, James R; Boutros, Paul C; Witte, Owen N
Journal Cell Rep Publication Year/Month 2021-Dec
PMID 34919800 PMCID PMC8660260
Affiliation + expend 1.Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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 TCRalphabeta 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 TCRalphabeta 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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