March 30, 2021

SARS-CoV-2 Variant B.1.1.7 Caused HLA-A2+ CD8+ T Cell Epitope Mutations for Impaired Cellular Immune Response

Category: Article Summary

Topic: Vaccines and Immunity

Keywords (Tags): immunity, variants

• [Pre-print, not peer-reviewed] The SARS-CoV-2 B.1.1.7 variant is associated with reduced CD8+ T cell activation due to at least two specific mutations in ORF1. The authors used algorithms to predict HLA-A2 binding epitopes in both the B.1.1.7 strain and the ancestral Wuhan strain and determined whether these epitopes could activate CD8+ T cells using an artificial antigen presentation system. Two mutations located in non-structural proteins of the B.1.1.7 variant (A1708D mutation in ORF1ab1707-1716 and I2230T mutation in ORF1ab2230-2238) were linked in the decreased activation of CD8+ T cells. The authors then constructed SARS-CoV-2 CD8+ tetramers based upon these predicted epitopes and used them to probe the CD8+ T cell memory from convalescent patients. They found that most CD8+ T cells from convalescent patients had an effector memory phenotype and furthermore there was substantially reduced recognition of the B.1.1.7 mutant epitopes.

Xiao et al. (Mar 29, 2021). SARS-CoV-2 Variant B.1.1.7 Caused HLA-A2+ CD8+ T Cell Epitope Mutations for Impaired Cellular Immune Response. Pre-print downloaded Mar 30 from https://doi.org/10.1101/2021.03.28.437363