The molecular mechanisms of CD8+ T cell responses to SARS-CoV-2 infection mediated by TCR-pMHC interactions

Front Immunol. 2024 Oct 10:15:1468456. doi: 10.3389/fimmu.2024.1468456. eCollection 2024.

Abstract

Cytotoxic CD8+ T lymphocytes (CTLs) have been implicated in the severity of COVID-19. The TCR-pMHC ternary complex, formed by the T cell receptor (TCR) and peptide-MHC (major histocompatibility complex), constitutes the molecular basis of CTL responses against SARS-CoV-2. While numerous studies have been conducted on T cell immunity, the molecular mechanisms underlying CTL-mediated immunity against SARS-CoV-2 infection have not been well elaborated. In this review, we described the association between HLA variants and different immune responses to SARS-CoV-2 infection, which may lead to varying COVID-19 outcomes. We also summarized the specific TCR repertoires triggered by certain SARS-CoV-2 CTL epitopes, which might explain the variations in disease outcomes among different patients. Importantly, we have highlighted the primary strategies used by SARS-CoV-2 variants to evade T-cell killing: disrupting peptide-MHC binding, TCR recognition, and antigen processing. This review provides valuable insights into the molecule mechanism of CTL responses during SARS-CoV-2 infection, aiding efforts to control the pandemic and prepare for future challenges.

Keywords: HLA; SARS-CoV-2; TCR repertoire; TCR-pHLA; TCR-pMHC; cytotoxic T lymphocytes (CTL); epitope; mutations.

Publication types

  • Review

MeSH terms

  • CD8-Positive T-Lymphocytes* / immunology
  • COVID-19* / immunology
  • COVID-19* / virology
  • Epitopes, T-Lymphocyte / immunology
  • HLA Antigens / immunology
  • Humans
  • Receptors, Antigen, T-Cell* / immunology
  • Receptors, Antigen, T-Cell* / metabolism
  • SARS-CoV-2* / immunology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Receptors, Antigen, T-Cell
  • Epitopes, T-Lymphocyte
  • HLA Antigens

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study is supported by the National Key Research and Development Program of China (Grants No. 2022YFC2304102 and 2022YFC2303300), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB0490000), the National Natural Science Foundation of China (Grant No. 82272301 and 32100745), Anhui Provincial Key Research and Development Project (Grant No. 2022i01020025), the Fundamental Research Funds for the Central Universities (WK9100000001), and USTC Research Funds of the Double First-Class Initiative (YD9100002056).