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

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 tified 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.

Automated summary

The baseline composition of T cells has a direct impact on the response to pathogens, and the precursor states of these cells are complex and not well defined. This study examined the baseline state of T cells specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in prepandemic blood samples. The data revealed a diverse range of preexisting memory states in these cells, with distinct features and potential for trafficking to barrier tissues. The study also found cross-reactivity between T cell clones and antigens from commensal bacteria, highlighting the importance of noninfectious exposures to shaping preexisting immunity to SARS-CoV-2.