JCI Insight (Mar 2022)

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components

  • Lichen Jing,
  • Xia Wu,
  • Maxwell P. Krist,
  • Tien-Ying Hsiang,
  • Victoria L. Campbell,
  • Christopher L. McClurkan,
  • Sydney M. Favors,
  • Lawrence A. Hemingway,
  • Charmie Godornes,
  • Denise Q. Tong,
  • Stacy Selke,
  • Angela C. LeClair,
  • Chu-Woo Pyo,
  • Daniel E. Geraghty,
  • Kerry J. Laing,
  • Anna Wald,
  • Michael Gale Jr.,
  • David M. Koelle

Journal volume & issue
Vol. 7, no. 6

Abstract

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SARS-CoV-2 provokes a robust T cell response. Peptide-based studies exclude antigen processing and presentation biology, which may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DCs to activate CD8 and CD4 T cells from convalescent people. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2–infected respiratory tract cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the Alpha, Beta, Gamma, and Delta variant lineages.

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