SARS-CoV-2 variant B.1.1.7 caused HLA-A2+CD8+T cell epitope mutations for impaired cellular immune response

SUMMARY The rapid spreading of the newly emerged SARS-CoV-2 variant, B.1.1.7, highlighted the requirements to better understand adaptive immune responses to this virus. Since CD8 + T cell responses play an important role in disease resolution and modulation in COVID-19 patients, it is essential to address whether these newly emerged mutations would result in altered immune responses. Here we evaluated the immune properties of the HLA-A2 restricted CD8 + T cell epitopes containing mutations from B.1.1.7, and furthermore performed a comprehensive analysis of the SARS-CoV-2 specific CD8 + T cell responses from COVID-19 convalescent patients and SARS-CoV-2 vaccinees recognizing the ancestral Wuhan strain compared to B.1.1.7. First, most of the predicted CD8 + T cell epitopes showed proper binding with HLA-A2, while epitopes from B.1.1.7 had lower binding capability than those from the ancestral strain. In addition, these peptides could effectively induced the activation and cytotoxicity of CD8 + T cells. Our results further showed that at least two site mutations in B.1.1.7 resulted in a decrease in CD8 + T cell activation and a possible immune evasion, namely A1708D mutation in ORF1ab 1707-1716 and I2230T mutation in ORF1ab 2230-2238 . Our current analysis provides information that contributes to the understanding of SARS-CoV-2-specific CD8 + T cell responses elicited by infection of mutated strains or vaccination. Graphical Abstract