Abstract
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.
Keywords: CD8 T cell; COVID-19; SARS-CoV-2; T cell; T cell receptors; immune escape; peptide-HLA; phylogenetic.
【저자키워드】 COVID-19, SARS-CoV-2, T cell, Immune escape, CD8 T cell, T cell receptors, peptide-HLA, Phylogenetic, 【초록키워드】 coronavirus, Mutation, spike, spike glycoprotein, human leukocyte antigen, Viral proteins, severe acute respiratory syndrome Coronavirus, CD8, variants, immune, Antigen, Protein, Epitopes, Cohort, T cell, Convalescent patients, Immune escape, SARS-CoV-2 variants, response, Lineage, glycoprotein, HLA, epitope, lineages, T cell epitope, convalescent patient, Next generation vaccine, SARS-CoV-2 spike, Frequency, T cell receptors, Phylogenetic, T cell epitopes, leukocyte, acute respiratory syndrome, Viral protein, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, individual, sequence, viral escape, cohorts, vaccine immunity, SARS-CoV-2 lineage, next generation vaccines, prevalent, new SARS-CoV-2, highlighting, for inclusion, mounted, 【제목키워드】 emergence, dominant,