Reference - Detail
| RRC ID | 55686 |
|---|---|
| Author | Maruhashi T, Okazaki IM, Sugiura D, Takahashi S, Maeda TK, Shimizu K, Okazaki T. |
| Title | LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII. |
| Journal | 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. |
| Volume | 19(12) |
| Pages | 1415-1426 |
| Published | 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 |
| Times Cited | 25 |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 54 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAJI(RCB1647) |