T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components.

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components.
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DOI:
10.1172/jci.insight.158126
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发表时间:
2022-03-22
期刊:
影响因子:
8
通讯作者:
Koelle DM
Koelle DM
中科院分区:
医学1区
文献类型:
--
作者:
Jing L;Wu X;Krist MP;Hsiang TY;Campbell VL;McClurkan CL;Favors SM;Hemingway LA;Godornes C;Tong DQ;Selke S;LeClair AC;Pyo CW;Geraghty DE;Laing KJ;Wald A;Gale M Jr;Koelle DM

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新冠病毒(SARS-CoV - 2)引发强烈的T细胞反应。基于肽段的研究排除了可能影响T细胞检测研究的抗原加工和呈递生物学因素。为了专注于对完整病毒和复杂抗原的反应,我们使用完整的新冠病毒以及全长蛋白质与树突状细胞(DCs)来激活康复者的CD8和CD4 T细胞。T细胞受体(TCR)测序显示扩增后部分受体库得以保留。由此产生的CD8 T细胞能够识别新冠病毒感染的呼吸道细胞,CD4 T细胞能够检测灭活的全病毒抗原。用覆盖蛋白质组的蛋白质/肽段阵列进行的特异性扫描显示,每个受试者的CD8 T细胞具有寡特异性,并且CD4 T细胞的特异性广度更高。一些使用新冠病毒富集的CD4 T细胞系可交叉识别完整的季节性冠状病毒(sCoV)抗原,并经过蛋白质、肽段和人类白细胞抗原(HLA)限制验证。相反,对于新冠病毒的一些变异株,包括阿尔法(Alpha)、贝塔(Beta)、伽马(Gamma)和德尔塔(Delta)变异株谱系中的刺突(S)表位,某些表位的识别消失。
SARS-CoV-2 provokes a robust T cell response. Peptide-based studies exclude antigen processing and presentation biology, which may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DCs to activate CD8 and CD4 T cells from convalescent people. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2–infected respiratory tract cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the Alpha, Beta, Gamma, and Delta variant lineages.
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