tetano
Editor, Senior Moderator
Cell
. 2022 Aug 4;185(16):2936-2951.e19.
doi: 10.1016/j.cell.2022.07.002. Epub 2022 Jul 14.
Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope
Garry Dolton[SUP] 1 [/SUP], Cristina Rius[SUP] 1 [/SUP], Md Samiul Hasan[SUP] 1 [/SUP], Aaron Wall[SUP] 1 [/SUP], Barbara Szomolay[SUP] 2 [/SUP], Enas Behiry[SUP] 1 [/SUP], Thomas Whalley[SUP] 3 [/SUP], Joel Southgate[SUP] 3 [/SUP], Anna Fuller[SUP] 1 [/SUP], COVID-19 Genomics UK (COG-UK) consortium; Théo Morin[SUP] 1 [/SUP], Katie Topley[SUP] 1 [/SUP], Li Rong Tan[SUP] 1 [/SUP], Philip J R Goulder[SUP] 4 [/SUP], Owen B Spiller[SUP] 1 [/SUP], Pierre J Rizkallah[SUP] 1 [/SUP], Lucy C Jones[SUP] 5 [/SUP], Thomas R Connor[SUP] 6 [/SUP], Andrew K Sewell[SUP] 7 [/SUP]
Affiliations
Abstract
We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein[SUB]269-277[/SUB] epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A[SUP]∗[/SUP]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[SUP]∗[/SUP]02[SUP]+[/SUP] 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.
Keywords: CD8 T cell; COVID-19; SARS-CoV-2; T cell; T cell receptors; immune escape; peptide-HLA; phylogenetic.
. 2022 Aug 4;185(16):2936-2951.e19.
doi: 10.1016/j.cell.2022.07.002. Epub 2022 Jul 14.
Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope
Garry Dolton[SUP] 1 [/SUP], Cristina Rius[SUP] 1 [/SUP], Md Samiul Hasan[SUP] 1 [/SUP], Aaron Wall[SUP] 1 [/SUP], Barbara Szomolay[SUP] 2 [/SUP], Enas Behiry[SUP] 1 [/SUP], Thomas Whalley[SUP] 3 [/SUP], Joel Southgate[SUP] 3 [/SUP], Anna Fuller[SUP] 1 [/SUP], COVID-19 Genomics UK (COG-UK) consortium; Théo Morin[SUP] 1 [/SUP], Katie Topley[SUP] 1 [/SUP], Li Rong Tan[SUP] 1 [/SUP], Philip J R Goulder[SUP] 4 [/SUP], Owen B Spiller[SUP] 1 [/SUP], Pierre J Rizkallah[SUP] 1 [/SUP], Lucy C Jones[SUP] 5 [/SUP], Thomas R Connor[SUP] 6 [/SUP], Andrew K Sewell[SUP] 7 [/SUP]
Affiliations
- PMID: 35931021
- PMCID: PMC9279490
- DOI: 10.1016/j.cell.2022.07.002
Abstract
We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein[SUB]269-277[/SUB] epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A[SUP]∗[/SUP]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[SUP]∗[/SUP]02[SUP]+[/SUP] 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.
Keywords: CD8 T cell; COVID-19; SARS-CoV-2; T cell; T cell receptors; immune escape; peptide-HLA; phylogenetic.