CD8+ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients

Vamsee Mallajosyula; Conner Ganjavi; Saborni Chakraborty; Alana M McSween; Ana Jimena Pavlovitch-Bedzyk; Julie Wilhelmy; Allison Nau; Monali Manohar; Kari C Nadeau; Mark M Davis

doi:10.1126/sciimmunol.abg5669

CD8⁺ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients

Sci Immunol. 2021 Jul 1;6(61):eabg5669. doi: 10.1126/sciimmunol.abg5669.

Authors

Affiliations

¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
² Department of Biology, Stanford University School of Humanities and Sciences, Stanford, CA 94305, USA.
³ Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.
⁴ Computational and Systems Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Sean N. Parker Center for Allergy and Asthma Research, Stanford University and Division of Pulmonary, Allergy, Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁶ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA. mmdavis@stanford.edu.
⁷ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁸ Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Abstract

A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a "memory" phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8⁺ T cells with these conserved specificities are much more abundant in COVID-19 patients with mild disease versus those with a more severe illness, suggesting a protective role.

Publication types

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

MeSH terms

CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
COVID-19 / immunology*
COVID-19 / pathology
Epitopes, T-Lymphocyte / immunology*
Female
Humans
Male
SARS-CoV-2 / immunology*
Severity of Illness Index*

Substances

Epitopes, T-Lymphocyte

Abstract

Publication types

MeSH terms

Substances

Grants and funding