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

• Published in: Cell reports. Medicine Vol. 4; no. 6; p. 101088
• Main Authors: Tarke, Alison, Zhang, Yun, Methot, Nils, Narowski, Tara M., Phillips, Elizabeth, Mallal, Simon, Frazier, April, Filaci, Gilberto, Weiskopf, Daniela, Dan, Jennifer M., Premkumar, Lakshmanane, Scheuermann, Richard H., Sette, Alessandro, Grifoni, Alba
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.06.2023; The Author(s)
• Subjects: CCC; Common Cold; Coronavirus; COVID-19; Cross Reactions; cross-reactivity; epitopes; HuCoV; Humans; NL63; OC43; sarbeco; SARS-CoV-2; T cells; T-Lymphocytes; epitopes; HuCoV; CCC; Coronavirus; sarbeco; OC43; cross-reactivity; T cells; NL63; common cold
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2023.101088

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. [Display omitted] •CD4 T cells recognize six immunodominant common cold coronavirus (CoV) antigens•Identify 165 epitopes and test 18 of these for cross-reactivity across CoVs•In 89% of instances, cross-reactivity was predicted by sequence conservation >67%•Previous CoV exposure likely affects T cell cross-reactivity to other CoVs Tarke et al. investigate CD4 T cells in common cold coronaviruses (CCCs) and find S, N, M, and nsp3 antigens are commonly recognized also in SARS2; 165 CCC CD4 T cell epitopes are identified. Cross-reactivity is observed between coronavirus (CoV) sequences with >67% homology in Alpha and Beta CoV groups.