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

tetano

Editor, Senior Moderator
JCI Insight


. 2022 Feb 8;e158126.
doi: 10.1172/jci.insight.158126. Online ahead of print.
T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components


Lichen Jing[SUP] 1 [/SUP], Xia Wu[SUP] 1 [/SUP], Maxwell P Krist[SUP] 1 [/SUP], Tien-Ying Hsiang[SUP] 2 [/SUP], Victoria L Campbell[SUP] 1 [/SUP], Christopher L McClurkan[SUP] 1 [/SUP], Sydney M Favors[SUP] 1 [/SUP], Lawrence Hemingway[SUP] 1 [/SUP], Charmie Godornes[SUP] 1 [/SUP], Denise Q Tong[SUP] 1 [/SUP], Stacy Selke[SUP] 3 [/SUP], Angela C LeClair[SUP] 1 [/SUP], Chul-Woo Pyo[SUP] 4 [/SUP], Daniel E Geraghty[SUP] 4 [/SUP], Kerry J Laing[SUP] 1 [/SUP], Anna Wald[SUP] 1 [/SUP], Michael Gale Jr[SUP] 2 [/SUP], David M Koelle[SUP] 1 [/SUP]



Affiliations

Abstract

SARS-CoV-2 provokes a robust T cell response. Peptide-based studies exclude antigen processing and presentation biology and 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 dendritic cells (DC) to activate CD8 and CD4 T cells from convalescent persons. 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.

Keywords: Antigen-presenting cells; Dendritic cells; Infectious disease; T cells.
 
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