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- Title
SARS-CoV-2-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses can originate from cross-reactive CMV-specific T cells.
- Authors
Pothast, Cilia R.; Dijkland, Romy C.; Thaler, Melissa; Hagedoorn, Renate S.; Kester, Michel G. D.; Wouters, Anne K.; Hiemstra, Pieter S.; van Hemert, Martijn J.; Gras, Stephanie; Falkenburg, J. H. Frederik; Heemskerk, Mirjam H. M.
- Abstract
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific CD4+ and CD8+ T cells in SARS-CoV-2-unexposed donors has been explained by the presence of T cells primed by other coronaviruses. However, based on the relatively high frequency and prevalence of cross-reactive T cells, we hypothesized cytomegalovirus (CMV) may induce these cross-reactive T cells. Stimulation of pre-pandemic cryo-preserved peripheral blood mononuclear cells (PBMCs) with SARS-CoV-2 peptides revealed that frequencies of SARS-CoV-2-specific T cells were higher in CMV-seropositive donors. Characterization of these T cells demonstrated that membrane-specific CD4+ and spike-specific CD8+ T cells originate from cross-reactive CMV-specific T cells. Spike-specific CD8+ T cells recognize SARS-CoV-2 spike peptide FVSNGTHWF (FVS) and dissimilar CMV pp65 peptide IPSINVHHY (IPS) presented by HLA-B*35:01. These dual IPS/FVS-reactive CD8+ T cells were found in multiple donors as well as severe COVID-19 patients and shared a common T cell receptor (TCR), illustrating that IPS/FVS-cross-reactivity is caused by a public TCR. In conclusion, CMV-specific T cells cross-react with SARS-CoV-2, despite low sequence homology between the two viruses, and may contribute to the pre-existing immunity against SARS-CoV-2.
- Subjects
T cells; SARS-CoV-2; IMMUNOSENESCENCE; MONONUCLEAR leukocytes; T cell receptors
- Publication
eLife, 2023, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.82050