1. Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2
- Author
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Tomonori Iyoda, Kanako Shimizu, Michihiro Hidaka, Masahiro Okada, Shin-ichiro Fujii, Shogo Ueda, Naoko Harada, An Sanpei, Mikako Shirouzu, Kazutaka Murayama, Miyuki Kato-Murayama, and Hiroshi Nakazato
- Subjects
QH301-705.5 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,T cell ,Receptors, Antigen, T-Cell ,Medicine (miscellaneous) ,Biology ,CD8-Positive T-Lymphocytes ,Cross Reactions ,Immunological memory ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,Article ,medicine ,Cytotoxic T cell ,Humans ,Avidity ,Biology (General) ,skin and connective tissue diseases ,Receptor ,Antigens, Viral ,Immunodominant Epitopes ,SARS-CoV-2 ,fungi ,T-cell receptor ,virus diseases ,COVID-19 ,Molecular biology ,body regions ,medicine.anatomical_structure ,Viral infection ,General Agricultural and Biological Sciences ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
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.
- Published
- 2021