9O4X

Gamma delta T cell receptor bound to CD1d

Summary for 9O4X

• Entry DOI: 10.2210/pdb9o4x/pdb
• Descriptor: Beta-2-microglobulin, T cell receptor delta chain, T cell receptor gamma chain, ... (8 entities in total)
• Functional Keywords: t cell receptor complex, gamma delta tcr, immune complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 92979.51

Authors

Rice, M.T.,Gully, B.S.,Rossjohn, J. (deposition date: 2025-04-09, release date: 2025-12-10, Last modification date: 2026-02-04)

Primary citation

Rice, M.T.,Gunasinghe, S.D.,Sok, C.L.,Pan, M.,Lay, C.S.,Gully, B.S.,Rossjohn, J.
gamma delta T cell receptor recognition of CD1d in a lipid-independent manner.
Nat Commun, 17:926-926, 2025

PubMed Abstract: The monomorphic antigen-presenting molecule CD1d presents lipid antigens to both αβ and γδ T cells. While type I natural killer T cells (NKT) display exquisite specificity for CD1d presenting α-galactosylceramide (α-GalCer), the extent of lipid specificity exhibited by CD1d-restricted γδ T cells remains unclear. Here, we demonstrate that human γδ T cell receptors (TCRs) can recognise CD1d in either a lipid-dependent or lipid-independent manner with weak to moderate affinity. Using small-angle X-Ray scattering, we find that γδ TCR-CD1d binding modality is conserved across distinct CD1d-restricted TCRs. In functional assays, CD1d γδ TCR affinity was a poor predictor of γδ T cell line activation. Moreover, CD1d presenting endogenous lipids was sufficient to stimulate T cell activation and induce γδ TCR-CD3 clustering and phosphorylation in a dose-dependent manner. Elongation of the γδ TCR-CD3 complex by the inclusion of the Cγ2 and Cγ3 -encoded constant domains perturbed cellular activation whilst maintaining the ability to form functional γδ TCR clusters. The crystal structure of a Vδ1 γδ TCR-CD1d complex showed that the γδ TCR sat atop of the CD1d antigen-binding cleft but made no contacts with the presented lipid antigen. These findings provide a molecular basis for lipid-independent CD1d recognition by γδ TCRs.

PubMed: 41457154
DOI: 10.1038/s41467-025-67653-0

Experimental method

X-RAY DIFFRACTION (2.86 Å)