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

By J. Mateus, Alba Grifoni, A. Tarke, John Sidney, S. Ramirez, J. Dan, Z. Burger, Stephen A. Rawlings, Davey M. Smith, E. Phillips and 16 more. Science, 2020

1,122 citations recorded by the source corpus.

Preexisting immune response to SARS-CoV-2 Robust T cell responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus occur in most individuals with coronavirus disease 2019 (COVID-19). Several studies have reported that some people who have not been exposed to SARS-CoV-2 have preexisting reactivity to SARS-CoV-2 sequences. The immunological mechanisms underlying this preexisting reactivity are not clear, but previous exposure to widely circulating common cold coronaviruses might be involved. Mateus et al. found that the preexisting reactivity against SARS-CoV-2 comes from memory T cells and that cross-reactive T cells can specifically recognize a SARS-CoV-2 epitope as well as the homologous epitope from a common cold coronavirus. These findings underline the importance of determining the impacts of preexisting immune memory in COVID-19 disease severity. Science, this issue p. 89 Preexisting immunity against SARS-CoV-2 can be derived from coronaviruses that cause the common cold. 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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/37423b62352ff6c2ca26ee97f3917b57997117c5

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In Infectious Diseases

Citations in the corpus

COVID-19 and the human innate immune system (2021, background): “Looking at the current pandemic entirely from a biological perspective and assuming that the majority of humankind does not have an extended cross-reaction to other viruses of the coronavirus family (Braun et al., 2020; Grifoni et al., 2020; Mateus et al., 2020), the introduction of SARS-CoV-2 into ”
Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients (2021, positive): “…hypothesis is that pre-existing immunological memory to ORF7 or ORF8 might have caused selective accelerated expansion of ORF7/8 T cells, because ORF7/8-specific T cells can be detected occasionally in archived PBMC samples collected from healthy individuals before 2019 (Mateus et al., 2020).”
Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, positive): “The prominence of M as a CD4 T cell target is intriguing, because M is a relatively small, multipass transmembrane protein without high-affinity class II restricted T cells in the naive repertoire (Mateus et al., 2020), suggesting that M is very highly expressed in vivo, or is made available to CD4 ”
COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing (2020, background): “One of the amino acid change was located in the Spike protein amino acid residue 222 which is also a potential site eliciting CD4+ T cell responses [36].”