1. Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope
- Author
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Dolton, Garry, Rius, Cristina, Hasan, Md Samiul, Wall, Aaron, Szomolay, Barbara, Behiry, Enas, Whalley, Thomas, Southgate, Joel, Fuller, Anna, COVID-19 Genomics UK (COG-UK) consortium, Morin, Théo, Topley, Katie, Tan, Li Rong, Goulder, Philip JR, Spiller, Owen B, Rizkallah, Pierre J, Jones, Lucy C, Connor, Thomas R, Sewell, Andrew K, Sewell, Andrew K [0000-0003-3194-3135], and Apollo - University of Cambridge Repository
- Subjects
HLA-A Antigens ,SARS-CoV-2 ,peptide-HLA ,Histocompatibility Antigens Class I ,immune escape ,Humans ,COVID-19 ,T cell ,Epitopes, T-Lymphocyte ,phylogenetic ,T cell receptors ,CD8-Positive T-Lymphocytes ,CD8 T cell - Abstract
We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein269-277 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.
- Published
- 2022