Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to 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. 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.

Automated summary

Identification of immunodominant epitopes in the SARS-CoV-2 spike region provides insight into cross-reactivity of CD8(+) T cells. Cross-reactive CD8(+) T cells are reduced in immunosuppressed patients with hematological malignancy. T-cell receptors isolated from selective pre-existing CD8(+) T cells exhibit diverse cross-reactivity at the single-cell level.