| RRC ID |
55686
|
| 著者 |
Maruhashi T, Okazaki IM, Sugiura D, Takahashi S, Maeda TK, Shimizu K, Okazaki T.
|
| タイトル |
LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII.
|
| ジャーナル |
Nat Immunol
|
| Abstract |
The success of tumor immunotherapy targeting the inhibitory co-receptors PD-1 and CTLA-4 has indicated that many other co-receptors might be potential druggable targets, despite limited information about their functional differences. Here we identified a unique target selectivity for the inhibitory co-receptor LAG-3 that was intrinsic to its immunoregulatory roles. Although LAG-3 has been reported to recognize major histocompatibility complex (MHC) class II, it did not recognize MHC class II universally; instead, we found that it selectively recognized stable complexes of peptide and MHC class II (pMHCII). LAG-3 did not directly interfere with interactions between the co-receptor CD4 and MHC class II or between the T cell antigen receptor and MHC class II. Instead, LAG-3 preferentially suppressed T cells responsive to stable pMHCII by transducing inhibitory signals via its intracellular region. Thus, LAG-3 might function more selectively than previously thought and thereby maintain tolerance to dominant autoantigens.
|
| 巻・号 |
19(12)
|
| ページ |
1415-1426
|
| 公開日 |
2018-12-1
|
| DOI |
10.1038/s41590-018-0217-9
|
| PII |
10.1038/s41590-018-0217-9
|
| PMID |
30349037
|
| MeSH |
Animals
Antigens, CD / chemistry
Antigens, CD / immunology*
CD4-Positive T-Lymphocytes / immunology*
Cell Line, Tumor
Histocompatibility Antigens Class II / immunology*
Humans
Lymphocyte Activation / immunology*
Lymphocyte Activation Gene 3 Protein
Mice
Molecular Conformation
|
| IF |
23.53
|
| 引用数 |
25
|
| リソース情報 |
| ヒト・動物細胞 |
RAJI(RCB1647) |
