7PBE

Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope

Summary for 7PBE

• Entry DOI: 10.2210/pdb7pbe/pdb
• Related: 7P3D
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Spike protein S1, ... (7 entities in total)
• Functional Keywords: mhc i, a02, wuhan epitope, sars-cov-2, spike protein, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 191536.10

Authors

Rizkallah, P.J.,Sewell, A.K.,Wall, A.,Fuller, A. (deposition date: 2021-08-02, release date: 2022-04-27, Last modification date: 2024-01-31)

Primary citation

Dolton, G.,Rius, C.,Hasan, M.S.,Wall, A.,Szomolay, B.,Behiry, E.,Whalley, T.,Southgate, J.,Fuller, A.,Morin, T.,Topley, K.,Tan, L.R.,Goulder, P.J.R.,Spiller, O.B.,Rizkallah, P.J.,Jones, L.C.,Connor, T.R.,Sewell, A.K.
Emergence of immune escape at dominant SARS-CoV-2 killer T cell epitope.
Cell, 185:2936-, 2022

PubMed Abstract: We studied the prevalent cytotoxic CD8 T cell response mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein epitope (sequence YLQPRTFLL) via the most frequent human leukocyte antigen (HLA) class I worldwide, HLA A02. 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 A02 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.

PubMed: 35931021
DOI: 10.1016/j.cell.2022.07.002

Experimental method

X-RAY DIFFRACTION (3 Å)