LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII
| Autor: | Daisuke Sugiura, Suzuka Takahashi, Taku Okazaki, Kenji Shimizu, Takeo K. Maeda, Il-mi Okazaki, Takumi Maruhashi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MHC class II biology Chemistry medicine.medical_treatment Immunology Immunotherapy Major histocompatibility complex Cell biology 03 medical and health sciences 030104 developmental biology Antigen Cell culture medicine biology.protein Immunology and Allergy Receptor Function (biology) Intracellular |
| Zdroj: | Nature Immunology. 19:1415-1426 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/s41590-018-0217-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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