The SARS-CoV-2 Omicron BA.1 spike G446S mutation potentiates antiviral T-cell recognition

Author:

Motozono ChihiroORCID,Toyoda Mako,Tan Toong Seng,Hamana HiroshiORCID,Goto Yoshihiko,Aritsu Yoshiki,Miyashita Yusuke,Oshiumi HiroyukiORCID,Nakamura Kimitoshi,Okada SeijiORCID,Udaka Keiko,Kitamatsu Mizuki,Kishi HiroyukiORCID,Ueno TakamasaORCID

Abstract

AbstractAlthough the Omicron variant of the SARS-CoV-2 virus shows resistance to neutralizing antibody, it retains susceptibility to the cellular immune response. Here we characterize vaccine-induced T cells specific for various SARS-CoV-2 variants and identified HLA-A*24:02-restricted CD8+ T cells that strongly suppress Omicron BA.1 replication in vitro. Mutagenesis analyses revealed that a G446S mutation, located just outside the N-terminus of the cognate epitope, augmented TCR recognition of this variant. In contrast, no enhanced suppression of replication is observed against cells infected with the prototype, Omicron BA.2, and Delta variants that express G446. The enhancing effect of the G446S mutation is lost when target cells are treated with inhibitors of tripeptidyl peptidase II, a protein that mediates antigen processing. These ex vivo analysis and in vitro results demonstrate that the G446S mutation in the Omicron BA.1 variant affects antigen processing/presentation and potentiates antiviral activity by vaccine-induced T cells, leading to enhanced T cell recognition towards emerging variants.

Funder

Takeda Science Foundation

Japan Agency for Medical Research and Development

MEXT | Japan Society for the Promotion of Science

An intramural grant from Kumamoto University COVID-19 Research Projects

IMAI MEMORIAL TRUST FOR AIDS RESERARCH Shin-Nihon Foundation of Advanced Medical Research

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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