Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope

We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein(269)(-)(277) epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A*02. The Spike P272L mutation that has arisen in at least 112 different SARS-CoV-2 lineages to date, including in lineages classified as variants of concern, was not recognized by the large CD8 T cell response seen across cohorts of HLA A*02(+) convalescent patients and individuals vaccinated against SARS-CoV-2, despite these responses comprising of over 175 different individual T cell receptors. Viral escape at prevalent T cell epitopes restricted by high frequency HLAs may be particularly problematic when vaccine immunity is focused on a single protein such as SARS-CoV-2 Spike, providing a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlighting the need for monitoring T cell escape in new SARS-CoV-2 variants.

Automated summary

This study examined the CD8 T cell response against a specific epitope of the Spike glycoprotein of SARS-CoV-2 and found that a specific mutation was not recognized by the majority of HLA A*02(+) convalescent patients and vaccinated individuals. This highlights the potential problem of viral escape at prevalent T cell epitopes restricted by high frequency HLAs and suggests the inclusion of multiple viral proteins in next generation vaccines. Monitoring T cell escape in new SARS-CoV-2 variants is crucial.