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TCR-pMHC 相互作用介导的 CD8 T 细胞对 SARS-CoV-2 感染的分子机制。

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

机构信息

Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

出版信息

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

DOI:10.3389/fimmu.2024.1468456
PMID:39450171
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499136/
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.

摘要

细胞毒性 CD8 T 淋巴细胞（CTL）被认为与 COVID-19 的严重程度有关。T 细胞受体（TCR）和肽-MHC（主要组织相容性复合体）形成的 TCR-pMHC 三元复合物是 CTL 对 SARS-CoV-2 反应的分子基础。虽然已经对 T 细胞免疫进行了大量研究，但 CTL 介导的针对 SARS-CoV-2 感染的免疫的分子机制尚未得到很好的阐述。在这篇综述中，我们描述了 HLA 变体与 SARS-CoV-2 感染不同免疫反应之间的关联，这可能导致 COVID-19 结局的不同。我们还总结了特定 SARS-CoV-2 CTL 表位触发的特定 TCR 库，这可能解释了不同患者疾病结局的差异。重要的是，我们强调了 SARS-CoV-2 变体逃避 T 细胞杀伤的主要策略：破坏肽-MHC 结合、TCR 识别和抗原加工。本综述为 SARS-CoV-2 感染期间 CTL 反应的分子机制提供了有价值的见解，有助于控制大流行并为未来的挑战做好准备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/d2e3b380cc80/fimmu-15-1468456-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/eb37aeb088ef/fimmu-15-1468456-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/7d401063cd23/fimmu-15-1468456-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/693821d50d5b/fimmu-15-1468456-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/fb2fe6b74068/fimmu-15-1468456-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/d2e3b380cc80/fimmu-15-1468456-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/eb37aeb088ef/fimmu-15-1468456-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/7d401063cd23/fimmu-15-1468456-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/693821d50d5b/fimmu-15-1468456-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/fb2fe6b74068/fimmu-15-1468456-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/180b/11499136/d2e3b380cc80/fimmu-15-1468456-g005.jpg

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