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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\n                    <jats:sup>+<\/jats:sup>\n                    and spike-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells originate from cross-reactive CMV-specific T cells. Spike-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.7554\/elife.82050","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T06:00:19Z","timestamp":1669010419000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.82050","source":"Crossref","is-referenced-by-count":38,"title":["SARS-CoV-2-specific CD4+ and CD8+ T cell responses can originate from cross-reactive CMV-specific T cells"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-3123","authenticated-orcid":true,"given":"Cilia R","family":"Pothast","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05xvt9f17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Hematology, Leiden University Medical Center","place":["Leiden, 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