Molecular characterization of HLA class II binding to the LAG‐3 T cell co‐inhibitory receptor
| العنوان: | Molecular characterization of HLA class II binding to the LAG‐3 T cell co‐inhibitory receptor |
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| المؤلفون: | Georgina H. Mason, David K. Cole, Frédéric Triebel, Awen Gallimore, Andrew James Godkin, Bruce J. MacLachlan, Alexander Greenshields-Watson |
| المصدر: | European Journal of Immunology |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Molecular immunology and signaling, LAG3, T-Lymphocytes, medicine.medical_treatment, T cell, Immunology, Cell, T cells, Receptors, Antigen, T-Cell, Biology, immune checkpoint inhibitors, Jurkat Cells, 03 medical and health sciences, 0302 clinical medicine, LAG‐3, Costimulatory and Inhibitory T-Cell Receptors, Downregulation and upregulation, Cancer immunotherapy, Antigens, CD, HLA Antigens, Cell Line, Tumor, Neoplasms, medicine, Humans, Immunology and Allergy, Basic, Receptor, Research Articles, cancer immunotherapy, Lymphocyte Activation Gene 3 Protein, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, CD4 Antigens, pHLA‐II, biology.protein, Research Article|Basic, Antibody, Function (biology), 030215 immunology |
| الوصف: | Immune checkpoint inhibitors (antibodies that block the T cell co‐inhibitory receptors PD‐1/PD‐L1 or CTLA‐4) have revolutionized the treatment of some forms of cancer. Importantly, combination approaches using drugs that target both pathways have been shown to boost the efficacy of such treatments. Subsequently, several other T cell inhibitory receptors have been identified for the development of novel immune checkpoint inhibitors. Included in this list is the co‐inhibitory receptor lymphocyte activation gene‐3 (LAG‐3), which is upregulated on T cells extracted from tumor sites that have suppressive or exhausted phenotypes. However, the molecular rules that govern the function of LAG‐3 are still not understood. Using surface plasmon resonance combined with a novel bead‐based assay (AlphaScreenTM), we demonstrate that LAG‐3 can directly and specifically interact with intact human leukocyte antigen class II (HLA‐II) heterodimers. Unlike the homologue CD4, which has an immeasurably weak affinity using these biophysical approaches, LAG‐3 binds with low micromolar affinity. We further validated the interaction at the cell surface by staining LAG‐3+ cells with pHLA‐II‐multimers. These data provide new insights into the mechanism by which LAG‐3 initiates T cell inhibition. We demonstrate that human LAG‐3 binds directly to peptide‐human leukocyte antigen class II complex (pHLA‐II) with low micromolar affinity. These findings provide new insights into the mechanism by which LAG‐3 initiates T cell inhibition and has implication for the development of novel immune checkpoint inhibitors for cancer immunotherapy. |
| وصف الملف: | application/pdf |
| تدمد: | 1521-4141 0014-2980 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::295dfce87346771adca4707fe21a976bTest https://doi.org/10.1002/eji.202048753Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....295dfce87346771adca4707fe21a976b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15214141 00142980 |
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