Resistance potential of the HLA-A2-restricted immunodominant SARS-CoV-2-specific CD8⁺ T cell receptor repertoire to antigenic drift.

ABSTRACT: A major concern of COVID-19 is immune escape. While T cells are implicated in protection against severe disease, direct evaluation of their capacity to specifically target SARS-CoV-2 variants remains limited. We aim to narrow this gap by profiling the ability of CD8⁺ T cells to recognize SARS-CoV-2 mutations after vaccination and observe a high degree of phenotype and repertoire diversity. To better understand the breadth of antigen repertoire coverage, we interrogate the ability of SARS-CoV-2 specific TCRs to bind all point mutations of the immunodominant HLA-A2:S_269-277 epitope. While mutation space coverage is surprisingly vast, specific substitutions are not recognized by the vaccine-elicited repertoire. Structural analyses reveal a TCR sequence-based antigen reco

SUBMITTER: Malone MJ 

PROVIDER: S-EPMC12820262 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature