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

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


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.

Keywords: CCC; Coronavirus; HuCoV; NL63; OC43; T cells; common cold; cross-reactivity; epitopes; sarbeco.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19*
  • Common Cold*
  • Cross Reactions
  • Humans
  • SARS-CoV-2
  • T-Lymphocytes