tetano
Editor, Senior Moderator
Elife
. 2022 Nov 21;11:e82050.
doi: 10.7554/eLife.82050. Online ahead of print.
SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses can originate from cross-reactive CMV-specific T cells
Cilia R Pothast[SUP] 1 [/SUP], Romy C Dijkland[SUP] 1 [/SUP], Melissa Thaler[SUP] 2 [/SUP], Renate S Hagedoorn[SUP] 1 [/SUP], Michel G D Kester[SUP] 1 [/SUP], Anne K Wouters[SUP] 1 [/SUP], Pieter S Hiemstra[SUP] 3 [/SUP], Martijn J van Hemert[SUP] 2 [/SUP], Stephanie Gras[SUP] 4 [/SUP], J H Frederik Falkenburg[SUP] 1 [/SUP], Mirjam H M Heemskerk[SUP] 1 [/SUP]
Affiliations
Abstract
Detection of SARS-coronavirus-2 (SARS-CoV-2) specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and spike-specific CD8[SUP]+[/SUP] T cells originate from cross-reactive CMV-specific T cells. Spike-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: human; immunology; inflammation.
. 2022 Nov 21;11:e82050.
doi: 10.7554/eLife.82050. Online ahead of print.
SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses can originate from cross-reactive CMV-specific T cells
Cilia R Pothast[SUP] 1 [/SUP], Romy C Dijkland[SUP] 1 [/SUP], Melissa Thaler[SUP] 2 [/SUP], Renate S Hagedoorn[SUP] 1 [/SUP], Michel G D Kester[SUP] 1 [/SUP], Anne K Wouters[SUP] 1 [/SUP], Pieter S Hiemstra[SUP] 3 [/SUP], Martijn J van Hemert[SUP] 2 [/SUP], Stephanie Gras[SUP] 4 [/SUP], J H Frederik Falkenburg[SUP] 1 [/SUP], Mirjam H M Heemskerk[SUP] 1 [/SUP]
Affiliations
- PMID: 36408799
- DOI: 10.7554/eLife.82050
Abstract
Detection of SARS-coronavirus-2 (SARS-CoV-2) specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and spike-specific CD8[SUP]+[/SUP] T cells originate from cross-reactive CMV-specific T cells. Spike-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
Keywords: human; immunology; inflammation.