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SARS-CoV-2 proteins

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    Suboptimal SARS-CoV-2-specific CD8 HGNC+ T-cell response associated with the prominent HLA-A HGNC*02:01 phenotype

    Authors: Jennifer R Habel; Thi H O Nguyen; Carolien E van de Sandt; Jennifer A Juno; Priyanka Chaurasia; Kathleen Wragg; Marios Koutsakos; Luca Hensen; Brendon Chua; Wuji Zhang; Hyon Xhi Tan; Katie L Flanagan; Denise Doolan; Joseph Torresi; Weisan Chen; Linda Wakim; Allen Cheng; Jan Petersen; Jamie Rossjohn; Adam K Wheatley; Stephen Kent; Louise Rowntree; Katherine Kedzierska

    doi:10.1101/2020.08.17.20176370 Date: 2020-08-19 Source: medRxiv

    An improved understanding of human T-cell-mediated immunity in COVID-19 MESHD is important if we are to optimize therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8 HGNC+ T-cell memory to shared peptides presented by common HLA types like HLA-A2. Following re-infection, cross-reactive CD8 HGNC+ T-cells enhance recovery and diminish clinical severity. Stimulating peripheral blood mononuclear cells from COVID-19 MESHD convalescent patients with overlapping peptides from SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD, Nucleocapsid and Membrane proteins led to the clonal expansion of SARS-CoV-2-specific CD8 HGNC+ and CD4 HGNC+ T-cells in vitro, with CD4 HGNC+ sets being typically robust. For CD8 HGNC+ T-cells taken directly ex vivo, we identified two HLA-A HGNC*02:01-restricted SARS-CoV-2 epitopes, A2/S269-277 and A2/Orf1ab3183-3191. Using peptide-HLA tetramer enrichment, direct ex vivo assessment of the A2/S269+ CD8 HGNC+ and A2/Orf1ab3183+ CD8 HGNC+ populations indicated that the more prominent A2/S269+ CD8 HGNC+ set was detected at comparable frequency (1.3x10-5) in acute and convalescent HLA-A HGNC*02:01+ patients. But, while the numbers were higher than those found in uninfected HLA-A HGNC*02:01+ donors (2.5x10-6), they were low when compared with frequencies for influenza-specific (A2/M158) and EBV-specific (A2/BMLF1280) (1.38x10-4) populations. Phenotypic analysis ex vivo of A2/S269+ CD8 HGNC+ T-cells from COVID-19 MESHD convalescents showed that A2/S269+ CD8 HGNC+ T-cells were predominantly negative for the CD38 HGNC, HLA-DR, PD-1 HGNC and CD71 HGNC activation markers, although the majority of total CD8 HGNC+ T-cells were granzyme and/or perforin-positive. Furthermore, the bias towards naive, stem cell memory and central memory A2/S269+ CD8 HGNC+ T-cells rather than effector memory populations suggests that SARS-CoV2 infection MESHD may be compromising CD8 HGNC+ T-cell activation. Priming with an appropriate vaccine may thus have great value for optimizing protective CD8 HGNC+ T-cell immunity in COVID-19 MESHD.

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MeSH Disease
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