Title

HLA-A

Document Type

Article

Publication Date

12-28-2021

Publication Title

Cell Rep

Keywords

seattle; washington; isb; covid-19; CD8-Positive T-Lymphocytes; COVID-19; Cell Culture Techniques; Coronavirus RNA-Dependent RNA Polymerase; Cross Reactions; Epitopes, T-Lymphocyte; HLA-A Antigens; HLA-A2 Antigen; Humans; Immunodominant Epitopes; Leukocytes, Mononuclear; RNA, Viral; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, alpha-beta; SARS-CoV-2; Spike Glycoprotein, Coronavirus

Abstract

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.

Department

Institute for Systems Biology

Department

Infectious Diseases

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