SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens

Sci Immunol. 2022 Oct 21;7(76):eabn3127. doi: 10.1126/sciimmunol.abn3127. Epub 2022 Oct 14.

Abstract

The baseline composition of T cells directly affects later response to pathogens, but the complexity of precursor states remains poorly defined. Here, we examined the baseline state of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in unexposed individuals. SARS-CoV-2-specific CD4+ T cells were identified in prepandemic blood samples by major histocompatibility complex (MHC) class II tetramer staining and enrichment. Our data revealed a substantial number of SARS-CoV-2-specific T cells that expressed memory phenotype markers. Integrated phenotypic analyses demonstrated diverse preexisting memory states that included cells with distinct polarization features and trafficking potential to barrier tissues. T cell clones generated from tetramer-labeled cells cross-reacted with antigens from commensal bacteria in the skin and gastrointestinal tract. Direct ex vivo tetramer staining for one spike-specific population showed a similar level of cross-reactivity to sequences from endemic coronavirus and commensal bacteria. These data highlight the complexity of precursor T cell repertoire and implicate noninfectious exposures to common microbes as a key factor that shapes human preexisting immunity to SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • COVID-19*
  • Humans
  • Immunologic Memory
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus
  • T-Lymphocytes

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2