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T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components.

Lichen JingXia WuMaxwell P KristTien-Ying HsiangVictoria L CampbellChristopher L McClurkanSydney M FavorsLawrence A HemingwayCharmie GodornesDenise Q TongStacy SelkeAngela C LeClairChu-Woo PyoDaniel E GeraghtyKerry J LaingAnna WaldMichael GaleDavid M Koelle
Published in: medRxiv : the preprint server for health sciences (2022)
SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2-infected respiratory cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the alpha, beta, gamma, and delta variant lineages.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • dendritic cells
  • induced apoptosis
  • binding protein
  • immune response
  • cell proliferation
  • dna methylation
  • signaling pathway
  • cell death
  • genome wide