Potential global impact of the N501Y mutation on MHC-II presentation and immune escape

The B.1.1.7 SARS-CoV-2 variant, characterized by the N501Y mutation, is rapidly emerging, raising concerns about its effectiveness on natural as well as vaccine-induced adaptive viral immunity at the population level. Since CD4 T cell responses are of critical importance to the antibody response, we examined the global effects of N501Y mutation on MHC-II presentation compared to the N501 wildtype and found poorer presentation across the majority of MHC-II alleles. This suggests that the N501Y mutation may not only diminish binding of antibodies to the RBD but also interfere with their production by weakening the cooperation between T and B cells, facilitating immune escape.