Abstract
ABSTRACTThe adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8 ‘killer’ T-cell response mounted against SARS-CoV-2 Spike269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A*02. The widespread Spike P272L mutation has arisen in at least 14 different SARS-CoV-2 lineages to date, including in lineages identified as variants of concern. P272L was common in the B.1.177 lineage associated with establishing the ‘second wave’ in Europe. The large CD8 T-cell response seen across a cohort of HLA A*02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L. Sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants.New in Version 2Updated as P272L now seen in 14 different SARS-CoV-2 lineages including the B.1.1.7/Alpha (UK variant) lineageAtomic structures of HLA A*02-YLQPRTFLL and HLA A*02-YLQLRTFLL addedPierre Rizkallah added as an author and author list changed to reflect the contributions of Aaron Wall and Anna Fuller to the newly added datasets
Publisher
Cold Spring Harbor Laboratory
Cited by
10 articles.
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