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.
SARS-CoV-2 vaccine immunogenicity is commonly evaluated by measuring antibody titers against the SARS-CoV-2 Spike (S) protein. Previously, inferior humoral vaccination responses in patients with lymphoid malignancies have been shown. 1 This can be attributed to immune defects caused by disease or treatment. NHL and CLL treated with CD20-and MM with CD38-directed therapies, leads to longlasting B-or plasma-cell depletion, respectively. CLL and MM are associated with hypogammaglobulinemia and aberrations in T-cell function. T-cell immunity is vital for viral clearance and long-lasting protection against COVID-19 after vaccination. 2 Moreover, high CD8 + T-cells contribute to COVID-19 survival in hematological patients. 3 Studies investigating T-cell responses after vaccination in patients with lymphoid malignancies are, however, scarce and results are conflicting. This leaves a knowledge gap, underlining the urgency of an in-depth and reproducible analysis of functional SARS-CoV-2 specific T-cell responses following vaccination in hematological patients. Patients. Adult patients diagnosed with CLL, NHL, or MM at two tertiary care centers in the Netherlands undergoing SARS-CoV-2 vaccination were included in the study. Serological and T-cell responses
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-reserved 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 and shared a common T cell receptor (TCR), illustrating that IPS/FVS-cross-reactivity is caused by a public TCR. Importantly, these cross-reactive T cells reduced spreading of SARS-CoV-2 in airway epithelial Calu-3 cells yet they were not phenotypically activated during late-stage COVID-19, indicating that cross-reactive T cells may more likely play a role during early stage of infection. 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.