SARS-CoV-2-specific T cell recognition toward emerging variants

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Cytotoxic T lymphocytes (CTLs) play an important role in the control of various viral infection. CTLs recognize a complex of HLA (human leukocyte antigen) class I molecule and epitope peptide derived from viral protein on the cell surface via T cell receptors and can destroy virally infected cells. It is becoming evident that SARS-CoV-2 specific T cells play a crucial role in the control of COVID-19. We characterized T cells specific for various SARS-CoV-2 variants and identified that a L452R mutation in the Delta spike protein evades HLA-A*24:02-restricted T cell responses and increases virus infectivity. In contrast, HLA-A*24:02-restricted T cells strongly suppresses Omicron BA.1 replication due to a G446S mutation, located just outside the N-terminus of the cognate epitope, in the Omicron BA.1 variant via enhanced antigen processing and presentation of the epitope. These data indicate that T cell specific for antigens derived from variable regions is highly susceptible for the mutation and its location. The detail analysis of antigen-specific T cell responses toward variants provides better insights for the rational design of vaccine antigens or immunotherapy to induce efficient cellular immunity against new emerging viruses/variants.