Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans

J Mateus, A Grifoni, A Tarke, J Sidney, SI Ramirez… - Science, 2020 - science.org
Many unknowns exist about human immune responses to the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2–reactive CD4+ T cells have
been reported in unexposed individuals, suggesting preexisting cross-reactive T cell
memory in 20 to 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 …
Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2–reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 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 preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and 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 coronavirus disease 2019 (COVID-19) disease.
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