TCR–pMHC bond conformation controls TCR ligand discrimination
| Autor: | Jian Qin, Wei Feng, Hans Schreiber, Yanran He, Chufan Cai, Huada Lian, Enfu Hui, Sobhan Roy, Dibyendu Kumar Sasmal, Jun Huang, Erin J. Adams, Peter Leung, Guoshuai Cao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD3 Complex ligand discrimination T-Lymphocytes Immunology Receptors Antigen T-Cell Bond conformation chemical and pharmacologic phenomena Article Mice 03 medical and health sciences 0302 clinical medicine Histocompatibility Antigens Immunoreceptor tyrosine-based activation motif Animals Immunology and Allergy Receptor Calcium signaling Mice Knockout Chemistry Cell Membrane T-cell receptor hemic and immune systems Single-molecule FRET Cellular immunity Single molecule FRET 030104 developmental biology Infectious Diseases Förster resonance energy transfer Membrane CD4 Antigens MHC class II Biophysics Phosphorylation T cell receptor 030215 immunology |
| Zdroj: | Cellular and Molecular Immunology |
| ISSN: | 2042-0226 1672-7681 |
| DOI: | 10.1038/s41423-019-0273-6 |
| Popis: | A major unanswered question is how a TCR discriminates between foreign and self-peptides presented on the APC surface. Here, we used in situ fluorescence resonance energy transfer (FRET) to measure the distances of single TCR–pMHC bonds and the conformations of individual TCR–CD3ζ receptors at the membranes of live primary T cells. We found that a TCR discriminates between closely related peptides by forming single TCR–pMHC bonds with different conformations, and the most potent pMHC forms the shortest bond. The bond conformation is an intrinsic property that is independent of the binding affinity and kinetics, TCR microcluster formation, and CD4 binding. The bond conformation dictates the degree of CD3ζ dissociation from the inner leaflet of the plasma membrane via a positive calcium signaling feedback loop to precisely control the accessibility of CD3ζ ITAMs for phosphorylation. Our data revealed the mechanism by which a TCR deciphers the structural differences among peptides via the TCR–pMHC bond conformation. |
| Databáze: | OpenAIRE |
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