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

V Mallajosyula, C Ganjavi, S Chakraborty… - Science …, 2021 - science.org
V Mallajosyula, C Ganjavi, S Chakraborty, AM McSween, AJ Pavlovitch-Bedzyk, J Wilhelmy…
Science immunology, 2021science.org
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 the 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 …
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 the 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 among coronaviruses are more abundant and tend to have a “memory” phenotype compared with those unique to SARS-CoV-2. Notably, CD8+ T cells with these conserved specificities are much more abundant in patients with mild COVID-19 versus those with a more severe illness, suggesting a protective role.
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