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

L Bartolo, S Afroz, YG Pan, R Xu, L Williams… - Science …, 2022 - science.org
L Bartolo, S Afroz, YG Pan, R Xu, L Williams, CF Lin, C Tanes, K Bittinger, ES Friedman
Science immunology, 2022science.org
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 …
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.
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