SARS-CoV-2-specific CD4+ and CD8+ T cell responses can originate from cross-reactive CMV-specific T cells
- Leiden University Medical Center, Netherlands
- Monash University, Australia
Abstract
Detection of SARS-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 relative high frequency and prevalence of cross-reactive T cells, we hypothesized CMV may induce these cross-reactive T cells. Stimulation of pre-pandemic cryo-preserved 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.
Data availability
Figure 1 - Source data 1 contains percentages underlying figure 1C-F. Figure 4 - Source data 1 contains the sequence data used to generate figures and the data have been deposited in SRA (NCBI) database under BioProjectID PRJNA891934.
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TCRa and TCRb sequences of HLA-B*35:01/IPS-isolated T cellsNCBI BioProject, PRJNA891934.
Article and author information
Author details
Funding
Health~Holland (LSHM19088)
- Mirjam HM Heemskerk
National Health and Medical Research Council (1159272)
- Stephanie Gras
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Bio-banked PBMCs were cryopreserved after informed consent from the respective donors, in accordance with the declaration of Helsinki. The samples from COVID-19 patients were part of a trial (NL8589) registered in the Dutch Trial Registry and approved by Medical Ethical Committee Leiden-Den Haag-Delft (NL73740.058.20).
Copyright
© 2022, Pothast et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SARS-CoV-2-specific CD4+ and CD8+ T cell responses can originate from cross-reactive CMV-specific T cells
eLife 11:e82050.
https://doi.org/10.7554/eLife.82050
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