Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans
View ORCID ProfileJose Mateus1, View ORCID ProfileAlba Grifoni1, View ORCID ProfileAlison Tarke1, View ORCID ProfileJohn Sidney1, View ORCID ProfileSydney I. Ramirez1,3, View ORCID ProfileJennifer M. Dan1,3,
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Science 04 Aug 2020:
eabd3871
DOI: 10.1126/science.abd3871
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.
