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

Chihiro Motozono (), Mako Toyoda, Toong Seng Tan, Hiroshi Hamana, Yoshihiko Goto, Yoshiki Aritsu, Yusuke Miyashita, Hiroyuki Oshiumi, Kimitoshi Nakamura, Seiji Okada, Keiko Udaka, Mizuki Kitamatsu, Hiroyuki Kishi and Takamasa Ueno ()
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Chihiro Motozono: Kumamoto University
Mako Toyoda: Kumamoto University
Toong Seng Tan: Kumamoto University
Hiroshi Hamana: University of Toyama
Yoshihiko Goto: Kumamoto University
Yoshiki Aritsu: Kindai University
Yusuke Miyashita: Kumamoto University
Hiroyuki Oshiumi: Kumamoto University
Kimitoshi Nakamura: Kumamoto University
Seiji Okada: Kumamoto University
Keiko Udaka: Kochi University
Mizuki Kitamatsu: Kindai University
Hiroyuki Kishi: University of Toyama
Takamasa Ueno: Kumamoto University

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Although 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.

Date: 2022
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DOI: 10.1038/s41467-022-33068-4

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