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

• Published in: Science Immunology 2021-07, Vol.6 (61)
• Main Authors: Mallajosyula, Vamsee, Ganjavi, Conner, Chakraborty, Saborni, McSween, Alana M, Pavlovitch-Bedzyk, Ana Jimena, Wilhelmy, Julie, Nau, Allison, Manohar, Monali, Nadeau, Kari C, Davis, Mark M
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 2470-9468
• DOI: 10.1126/sciimmunol.abg5669

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.