Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope

Cell. 2022 Aug 4;185(16):2936-2951.e19. doi: 10.1016/j.cell.2022.07.002. Epub 2022 Jul 14.

Abstract

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as "variants of concern," was not recognized by the large CD8 T cell response seen across cohorts of HLA A02+ convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Keywords: CD8 T cell; COVID-19; SARS-CoV-2; T cell; T cell receptors; immune escape; peptide-HLA; phylogenetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes
  • COVID-19*
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Histocompatibility Antigens Class I
  • Humans
  • SARS-CoV-2*

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Histocompatibility Antigens Class I

Supplementary concepts

  • SARS-CoV-2 variants