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

Alison Tarke; Yun Zhang; Nils Methot; Tara M Narowski; Elizabeth Phillips; Simon Mallal; April Frazier; Gilberto Filaci; Daniela Weiskopf; Jennifer M Dan; Lakshmanane Premkumar; Richard H Scheuermann; Alessandro Sette; Alba Grifoni

doi:10.1016/j.xcrm.2023.101088

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.

Authors

Affiliations

¹ 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.
² J. Craig Venter Institute, La Jolla, CA 92037, USA.
³ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
⁴ Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7290, USA.
⁵ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA 6150, Australia.
⁶ Center of Excellence for Biomedical Research, Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy; Biotherapy Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
⁷ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.
⁸ J. Craig Venter Institute, La Jolla, CA 92037, USA; Department of Pathology, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address: rscheuermann@jcvi.org.
⁹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA. Electronic address: alex@lji.org.
¹⁰ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA. Electronic address: agrifoni@lji.org.

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.

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

Abstract

Publication types

MeSH terms

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