Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
In summary, here we identified more than 140 human T cell epitopes derived from across the genome of SARS-CoV-2. We provide direct evidence that numerous CD4+ T cells that react to SARS-CoV-2 epitopes actually cross-react with corresponding homologous sequences from any of multiple different commonly circulating HCoVs, and that these reactive cells are largely canonical memory CD4+ T cells. These finding of cross-reactive HCoV T cell specificities are stark contrast to HCoV neutralizing antibodies, which are HCoV species-specific and did not show cross-reactivity against SARS-CoV-2 RBD (33–35). Based on these data, it is plausible to hypothesize that pre-existing cross-reactive HCoV CD4+ T cell memory in some donors could be a contributing factor to variations in COVID-19 patient disease outcomes, but this is at present highly speculative (36).
Abstract
Many unknowns exist about human immune responses to the SARS-CoV-2 virus. SARS-CoV-2 reactive CD4+ T cells have been reported in unexposed individuals, suggesting pre-existing cross-reactive T cell memory in 20-50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of pre-existing memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63, or HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in COVID-19 disease.
BY JOSE MATEUS, ALBA GRIFONI, ALISON TARKE, JOHN SIDNEY, SYDNEY I. RAMIREZ, JENNIFER M. DAN, ZOE C. BURGER, STEPHEN A. RAWLINGS, DAVEY M. SMITH, ELIZABETH PHILLIPS, SIMON MALLAL, MARSHALL LAMMERS, PAUL RUBIRO, LORENZO QUIAMBAO, AARON SUTHERLAND, ESTHER DAWEN YU, RICARDO DA SILVA ANTUNES, JASON GREENBAUM, APRIL FRAZIER, ALENA J. MARKMANN, LAKSHMANANE PREMKUMAR, ARAVINDA DE SILVA, BJOERN PETERS, SHANE CROTTY, ALESSANDRO SETTE, DANIELA WEISKOPF
PUBLISHED ONLINE
Source: http://gmopundit.blogspot.com/2020/09/selective-and-cross-reactive-sars-cov-2.html
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