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Title | Structures of human γδ T cell receptor-CD3 complex. |
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Journal, issue, pages | Nature, Year 2024 |
Publish date | Apr 24, 2024 |
Authors | Weizhi Xin / Bangdong Huang / Ximin Chi / Yuehua Liu / Mengjiao Xu / Yuanyuan Zhang / Xu Li / Qiang Su / Qiang Zhou / |
PubMed Abstract | Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse ...Gamma delta (γδ) T cells, a unique T cell subgroup, are crucial in various immune responses and immunopathology. The γδ T cell receptor (TCR), generated by γδ T cells, recognizes a diverse range of antigens independently of the major histocompatibility complex. The γδ TCR associates with CD3 subunits, initiating T cell activation and holding great potential in immunotherapy. Here, we report the structures of two prototypical human Vγ9Vδ2 and Vγ5Vδ1 TCR-CD3 complexes, unveiling two distinct assembly mechanisms that depend on Vγ usage. The Vγ9Vδ2 TCR-CD3 complex is monomeric, with considerable conformational flexibility in the TCRγ/TCRδ extracellular domain (ECD) and connecting peptides (CPs). The length of CPs regulates the ligand association and T cell activation. Additionally, a cholesterol-like molecule wedges into the transmembrane region, exerting an inhibitory role in TCR signaling. The Vγ5Vδ1 TCR-CD3 complex displays a dimeric architecture, where two protomers nestle back-to-back via their Vγ5 domains of TCR ECDs. Our biochemical and biophysical assays further corroborate the dimeric structure. Importantly, the dimeric form of the Vγ5Vδ1 TCR is essential for T cell activation. These findings reveal organizing principles of the γδ TCR-CD3 complex, providing insights into the γδ TCR unique properties and facilitating immunotherapeutic interventions. |
External links | Nature / PubMed:38657677 |
Methods | EM (single particle) |
Resolution | 3.0 - 9.5 Å |
Structure data | EMDB-36147, PDB-8jbv: EMDB-36149, PDB-8jc0: EMDB-36152: Vgamma5 Vdelta1 TCR complex (MPDI/TMDI) EMDB-36153: Vgamma5 Vdelta1 TCR complex (MPDII/TMDII) EMDB-36155: Vgamma5 Vdelta1 TCR complex (MPD/TMD) EMDB-36156, PDB-8jcb: EMDB-37904, PDB-8wxe: EMDB-37914, PDB-8wy0: EMDB-37929, PDB-8wyi: EMDB-39128, PDB-8yc0: EMDB-39359: T cell receptor V delta2 V gamma9 in GDN (DeepEMhancer) EMDB-39361: Vgamma5 Vdelta1 TCR complex (MPDI/TMDI, DeepEMhancer) EMDB-39362: Vgamma5 Vdelta1 TCR complex (MPDII/TMDII, DeepEMhancer) EMDB-39363: V gamma9 V delta2 TCR and CD3 complex in LMNG (DeepEMhancer) EMDB-39367: Vgamma5 Vdelta1 TCR-CD3 complex (EH mutant, DeepEMhancer) EMDB-39368: Extracellular domain of Vgamma5 Vdelta1 TCR (DeepEMhancer) |
Chemicals | ChemComp-CLR: |
Source |
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Keywords | IMMUNE SYSTEM / Receptor / immunity / immune |