人类 T 细胞识别普通感冒冠状病毒的靶点和交叉反应性。

Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

机构信息

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Experimental Medicine and Center of Excellence for Biomedical Research (CEBR), University of Genoa, 16132 Genoa, Italy.

J. Craig Venter Institute, La Jolla, CA 92037, USA.

出版信息

Cell Rep Med. 2023 Jun 20;4(6):101088. doi: 10.1016/j.xcrm.2023.101088. Epub 2023 May 29.

DOI:10.1016/j.xcrm.2023.101088

PMID:37295422

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10242702/

Abstract

The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.

摘要

冠状病毒（CoV）家族包括几种感染人类的病毒，这凸显了探索泛 CoV 疫苗策略以提供广泛适应性免疫保护的重要性。我们分析了大流行前样本中针对代表性的 Alpha（NL63）和 Beta（OC43）普通感冒 CoV（CCCs）的 T 细胞反应。S、N、M 和 nsp3 抗原是免疫优势抗原，这与严重急性呼吸综合征 2（SARS2）一样，而 nsp2 和 nsp12 是 Alpha 或 Beta 特异性的。我们进一步鉴定了 78 个 OC43 和 87 个 NL63 特异性表位，并且对于其中的一部分表位，我们评估了 T 细胞识别来自属于 AlphaCoV、sarbecoCoV 和 Beta-non-sarbecoCoV 组的代表性病毒的序列的能力。我们发现 Alpha 和 Beta 组内存在 T 细胞交叉反应性，在 89%的情况下与序列保守性>67%相关。然而，尽管存在保守性，但 sarbecoCoV 观察到的交叉反应性有限，表明先前的 CoV 暴露是决定交叉反应性的一个因素。总体而言，这些结果为开发未来的泛 CoV 疫苗提供了重要的见解。