PMID- 35931021 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20240306 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 185 IP - 16 DP - 2022 Aug 4 TI - Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope. PG - 2936-2951.e19 LID - S0092-8674(22)00849-2 [pii] LID - 10.1016/j.cell.2022.07.002 [doi] AB - 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. CI - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Dolton, Garry AU - Dolton G AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Rius, Cristina AU - Rius C AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Hasan, Md Samiul AU - Hasan MS AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Wall, Aaron AU - Wall A AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Szomolay, Barbara AU - Szomolay B AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK; Systems Immunology Research Institute, Cardiff University, CF14 4XN Cardiff, Wales, UK. FAU - Behiry, Enas AU - Behiry E AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Whalley, Thomas AU - Whalley T AD - School of Biosciences, Cardiff University, CF10 3AX Cardiff, Wales, UK. FAU - Southgate, Joel AU - Southgate J AD - School of Biosciences, Cardiff University, CF10 3AX Cardiff, Wales, UK. FAU - Fuller, Anna AU - Fuller A AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. CN - COVID-19 Genomics UK (COG-UK) consortium FAU - Morin, Theo AU - Morin T AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Topley, Katie AU - Topley K AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Tan, Li Rong AU - Tan LR AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Goulder, Philip J R AU - Goulder PJR AD - Department of Paediatrics, University of Oxford, OX3 9DU Oxford, England, UK. FAU - Spiller, Owen B AU - Spiller OB AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Rizkallah, Pierre J AU - Rizkallah PJ AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK. FAU - Jones, Lucy C AU - Jones LC AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK; Centre for Clinical Research, Royal Glamorgan Hospital, Ynysmaerdy CF72 8XR, UK. FAU - Connor, Thomas R AU - Connor TR AD - Systems Immunology Research Institute, Cardiff University, CF14 4XN Cardiff, Wales, UK; School of Biosciences, Cardiff University, CF10 3AX Cardiff, Wales, UK; Pathogen genomics Unit, Public Health Wales NHS Trust, CF14 4XW Cardiff, Wales, UK. Electronic address: connortr@cardiff.ac.uk. FAU - Sewell, Andrew K AU - Sewell AK AD - Division of Infection and Immunity, Cardiff University School of Medicine, CF14 4XN Cardiff, Wales, UK; Systems Immunology Research Institute, Cardiff University, CF14 4XN Cardiff, Wales, UK. Electronic address: sewellak@cardiff.ac.uk. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - MC_PC_19027/MRC_/Medical Research Council/United Kingdom GR - MR/L015080/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220714 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - SARS-CoV-2 variants SB - IM MH - CD8-Positive T-Lymphocytes MH - *COVID-19 MH - Epitopes, T-Lymphocyte MH - HLA-A Antigens MH - Histocompatibility Antigens Class I MH - Humans MH - *SARS-CoV-2 PMC - PMC9279490 OTO - NOTNLM OT - CD8 T cell OT - COVID-19 OT - SARS-CoV-2 OT - T cell OT - T cell receptors OT - immune escape OT - peptide-HLA OT - phylogenetic COIS- Declaration of interests The authors declare no competing interests in regard to this work. EDAT- 2022/08/06 06:00 MHDA- 2022/08/10 06:00 PMCR- 2022/08/04 CRDT- 2022/08/05 18:33 PHST- 2021/07/15 00:00 [received] PHST- 2022/05/08 00:00 [revised] PHST- 2022/07/07 00:00 [accepted] PHST- 2022/08/05 18:33 [entrez] PHST- 2022/08/06 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/08/04 00:00 [pmc-release] AID - S0092-8674(22)00849-2 [pii] AID - 10.1016/j.cell.2022.07.002 [doi] PST - ppublish SO - Cell. 2022 Aug 4;185(16):2936-2951.e19. doi: 10.1016/j.cell.2022.07.002. Epub 2022 Jul 14.