Abstract
It is critically important to understand how the adaptive immune response, elicited by vaccination or infection, recognizes SARS-CoV-2. This is especially true when considering the challenges to the immune response posed by variant evolution. Herein, we summarize our work aimed at characterizing the magnitude of the CD4(+) and CD8(+) T cell responses to SARS-CoV-2, the proteins most frequently recognized, and the associated T cell epitope repertoire. This work formed the foundation for our most recent studies aimed at understanding and predicting the ability of T cell responses induced by SARS-CoV-2 infection or vaccination to subsequently cross-recognize novel SARS-CoV-2 variants. We found that T cell responses are remarkably preserved and able to cross-recognize SARS-CoV-2 variants, from Alpha to Omicron. This is distinct from what has been observed for the SARS-CoV-2- specific antibody and B cell responses. This body of work, supported by independent studies carried out by other groups, suggests that T cells may contribute to a second line of defense against infection while also limiting viral spread and, thus, disease severity.