SARS-CoV-2-specific CD8 + T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific CD8 + T cells are converted to functionally competent T cells cross-reactive to SARS-CoV-2. Here, we identified the HLA-A24-high binding, immunodominant epitopes in SARS-CoV-2 spike region that can be recognized by seasonal coronavirus-specific CD8 + T cells from HLA-A24 + UHDs. Cross-reactive CD8 + T cells were clearly reduced in patients with hematological malignancy, who are usually immunosuppressed, compared to those in UHDs. Furthermore, we showed that CD8 + T cells in response to a selected dominant epitope display multifunctionality and cross-functionality across HCoVs in HLA-A24 + donors. Cross-reactivity of T-cell receptors isolated from them exhibited selective diversity at the single-cell level. Taken together, when stimulated well by immunodominant epitopes, selective pre-existing CD8 + T cells with high functional avidity may be cross-reactive against SARS-CoV-2. Kanako Shimizu et al. identify HLA-A24 high-binding epitopes in the SARS-CoV-2 spike region and investigate their cross-reactivity with CD8 + T cell receptors. These results provide further insight into CD8 + T cell cross-reactivity toward SARS-CoV-2 and may be useful in future strategies for vaccine development.
【저자키워드】 viral infection, Immunological memory, 【초록키워드】 SARS-CoV-2, Vaccine development, coronavirus, Hematological malignancy, CD8, cross-reactivity, T cell, Patient, T-cell receptor, donors, epitope, immunodominant epitopes, dominant epitope, binding, SARS-CoV-2 spike, T cell receptors, Immunosuppressed, cross-reactive, selective, single-cell level, immunodominant epitope, healthy donor, stimulated, selected, identify, detectable, reduced, exhibited, functional, competent, Shimizu, the SARS-CoV-2, 【제목키워드】 SARS-CoV-2, TCR, identification, Cytotoxic T cell, cross-reactive, competent,