| RRC ID |
73691
|
| 著者 |
Ogura H, Gohda J, Lu X, Yamamoto M, Takesue Y, Son A, Doi S, Matsushita K, Isobe F, Fukuda Y, Huang TP, Ueno T, Mambo N, Murakami H, Kawaguchi Y, Inoue JI, Shirai K, Yamasaki S, Hirata JI, Ishido S.
|
| タイトル |
Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Although the importance of virus-specific cytotoxic T lymphocytes (CTL) in virus clearance is evident in COVID-19, the characteristics of virus-specific CTLs related to disease severity have not been fully explored. Here we show that the phenotype of virus-specific CTLs against immunoprevalent epitopes in COVID-19 convalescents might differ according to the course of the disease. We establish a cellular screening method that uses artificial antigen presenting cells, expressing HLA-A*24:02, the costimulatory molecule 4-1BBL, SARS-CoV-2 structural proteins S, M, and N and non-structural proteins ORF3a and nsp6/ORF1a. The screen implicates SARS-CoV-2 M protein as a frequent target of IFNγ secreting CD8+ T cells, and identifies M198-206 as an immunoprevalent epitope in our cohort of HLA-A*24:02 positive convalescent COVID-19 patients recovering from mild, moderate and severe disease. Further exploration of M198-206-specific CD8+ T cells with single cell RNA sequencing reveals public TCRs in virus-specific CD8+ T cells, and shows an exhausted phenotype with less differentiated status in cells from the severe group compared to cells from the moderate group. In summary, this study describes a method to identify T cell epitopes, indicate that dysfunction of virus-specific CTLs might be an important determinant of clinical outcomes.
|
| 巻・号 |
13(1)
|
| ページ |
7063
|
| 公開日 |
2022-12-16
|
| DOI |
10.1038/s41467-022-34655-1
|
| PII |
10.1038/s41467-022-34655-1
|
| PMID |
36526616
|
| PMC |
PMC9758236
|
| MeSH |
CD8-Positive T-Lymphocytes*
COVID-19*
Epitopes, T-Lymphocyte
HLA-A Antigens
Humans
SARS-CoV-2
T-Lymphocytes, Cytotoxic
|
| IF |
12.121
|
| リソース情報 |
| 遺伝子材料 |
Human HLA-A*24:02:01 cDNA (RDB02871) |
