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

tetano

Editor, Senior Moderator
Sci Immunol


. 2022 Jul 14;eabn3127.
doi: 10.1126/sciimmunol.abn3127. Online ahead of print.
SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens


Laurent Bartolo[SUP] 1 [/SUP], Sumbul Afroz[SUP] 1 [/SUP], Yi-Gen Pan[SUP] 1 [/SUP], Ruozhang Xu[SUP] 1 2 [/SUP], Lea Williams[SUP] 1 2 [/SUP], Chin-Fang Lin[SUP] 1 [/SUP], Ceylan Tanes[SUP] 3 [/SUP], Kyle Bittinger[SUP] 3 [/SUP], Elliot S Friedman[SUP] 4 [/SUP], Phyllis A Gimotty[SUP] 5 [/SUP], Gary D Wu[SUP] 4 [/SUP], Laura F Su[SUP] 1 2 [/SUP]



Affiliations

Abstract

The baseline composition of T cells directly impacts later response to pathogens, but the complexity of precursor states remains poorly defined. Here, we examined the baseline state of SARS-CoV-2-specific T cells in unexposed individuals. SARS-CoV-2-specific CD4[SUP]+[/SUP] T cells were identified in pre-pandemic blood samples by class II peptide-MHC 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 pre-existing memory states that included cells with distinct polarization states 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 non-infectious exposures to common microbes as a key factor that shapes human pre-existing immunity to SARS-CoV-2.
 
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