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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

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

Pavlo A Nesterenko1, Jami McLaughlin2, Brandon L Tsai3

  • 1Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Cell Reports
|December 17, 2021
PubMed

Insights

Researchers identified conserved SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) targets for CD8+ T cells. These T cells cross-react with common cold coronaviruses, suggesting potential for broad immunity.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8+ T cell cross-reactivity and direct target cell killing are not well understood.
  • T cell receptors (TCRs) can be isolated and overexpressed in allogeneic cells for comprehensive T cell reactivity profiling.

Purpose of the Study:

  • To investigate the reactivity of SARS-CoV-2-specific CD8+ T cells.
  • To identify conserved viral targets for T cell-mediated immunity.
  • To explore the potential for cross-reactivity with other coronaviruses.

Main Methods:

  • Identification of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as a highly conserved viral protein.
  • Single-cell TCRαβ sequencing in human leukocyte antigen (HLA)-A*02:01-restricted, RdRp-specific T cells from SARS-CoV-2-unexposed individuals.
  • Engineering target cell lines to express full-length RdRp for T cell killing assays.

Main Results:

  • SARS-CoV-2 RdRp was identified as a highly conserved viral component.
  • TCRαβ constructs derived from RdRp-specific T cells effectively killed RdRp-expressing target cells.
  • Three TCR constructs demonstrated recognition of homologous epitopes from common cold coronaviruses.

Conclusions:

  • CD8+ T cells can recognize evolutionarily diverse coronaviruses, including SARS-CoV-2 and common cold strains.
  • Targeting conserved viral epitopes, such as those in RdRp, may induce long-term immunity.
  • Analysis of individual TCR clones can aid in defining vaccine epitopes for broad coronavirus protection.
Keywords:
CD8COVID-19SARS-CoV-2T cellsTCRantigencell therapyimmune responsesingle-cellspecific

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