tetano
Editor, Senior Moderator
Commun Biol
. 2021 Dec 2;4(1):1365.
doi: 10.1038/s42003-021-02885-6.
Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2
Kanako Shimizu[SUP] 1 [/SUP], Tomonori Iyoda[SUP] 1 [/SUP], An Sanpei[SUP] 1 [/SUP], Hiroshi Nakazato[SUP] 1 [/SUP], Masahiro Okada[SUP] 1 [/SUP], Shogo Ueda[SUP] 1 [/SUP], Miyuki Kato-Murayama[SUP] 2 [/SUP], Kazutaka Murayama[SUP] 2 3 [/SUP], Mikako Shirouzu[SUP] 2 [/SUP], Naoko Harada[SUP] 4 [/SUP], Michihiro Hidaka[SUP] 4 [/SUP], Shin-Ichiro Fujii[SUP] 5 6 [/SUP]
Affiliations
Abstract
SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T cells from HLA-A24[SUP]+[/SUP] UHDs. Cross-reactive CD8[SUP]+[/SUP] T cells were clearly reduced in patients with hematological malignancy, who are usually immunosuppressed, compared to those in UHDs. Furthermore, we showed that CD8[SUP]+[/SUP] T cells in response to a selected dominant epitope display multifunctionality and cross-functionality across HCoVs in HLA-A24[SUP]+[/SUP] 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[SUP]+[/SUP] T cells with high functional avidity may be cross-reactive against SARS-CoV-2.
. 2021 Dec 2;4(1):1365.
doi: 10.1038/s42003-021-02885-6.
Identification of TCR repertoires in functionally competent cytotoxic T cells cross-reactive to SARS-CoV-2
Kanako Shimizu[SUP] 1 [/SUP], Tomonori Iyoda[SUP] 1 [/SUP], An Sanpei[SUP] 1 [/SUP], Hiroshi Nakazato[SUP] 1 [/SUP], Masahiro Okada[SUP] 1 [/SUP], Shogo Ueda[SUP] 1 [/SUP], Miyuki Kato-Murayama[SUP] 2 [/SUP], Kazutaka Murayama[SUP] 2 3 [/SUP], Mikako Shirouzu[SUP] 2 [/SUP], Naoko Harada[SUP] 4 [/SUP], Michihiro Hidaka[SUP] 4 [/SUP], Shin-Ichiro Fujii[SUP] 5 6 [/SUP]
Affiliations
- PMID: 34857854
- DOI: 10.1038/s42003-021-02885-6
Abstract
SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells are scarce but detectable in unexposed healthy donors (UHDs). It remains unclear whether pre-existing human coronavirus (HCoV)-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T cells from HLA-A24[SUP]+[/SUP] UHDs. Cross-reactive CD8[SUP]+[/SUP] T cells were clearly reduced in patients with hematological malignancy, who are usually immunosuppressed, compared to those in UHDs. Furthermore, we showed that CD8[SUP]+[/SUP] T cells in response to a selected dominant epitope display multifunctionality and cross-functionality across HCoVs in HLA-A24[SUP]+[/SUP] 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[SUP]+[/SUP] T cells with high functional avidity may be cross-reactive against SARS-CoV-2.