Abstract SARS-CoV-2-specific CD8+ T cells are detectable in infected individuals but are low in unexposed healthy donors (UHD). Little is known about whether pre-existing human coronavirus (HCoV)-specific CD8+ T cells are converted to functionally competent T cells cross-reactive to SARS-CoV-2. Induction of cross-reactive immunity requires the recognition of multiple epitopes. Here, we show that SARS-CoV-2-specific T cells elicited in response to a selected dominant epitope are multifunctional and respond to various HCoVs in UHD. TCRαβ chains from each T cell clone were identified; TCRαβ-transduced T cells responded broadly to the relevant epitopes on several HCoVs, thus implying that TCRαβ may exhibit selective diversity at the single-cell level. We further defined four sets of optimal SARS-CoV-2-peptides and demonstrated the response of CD8+ T cells even in hematological malignant patients. Together, the proposed epitopes inducing pre-existing CD8+ T cells to cross-react with SARS-CoV-2 may be beneficial in vaccine development.