7LLI

Stimulatory immune receptor protein complex

Summary for 7LLI

• Entry DOI: 10.2210/pdb7lli/pdb
• Related: 7LLJ
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, T cell receptor gamma variable 8, ... (5 entities in total)
• Functional Keywords: immune receptor complex, metabolite immunity, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 191549.53

Authors

Rice, M.T.,Littler, D.R.,Rossjohn, J.,Gully, B.S. (deposition date: 2021-02-04, release date: 2021-11-17, Last modification date: 2024-11-13)

Primary citation

Rice, M.T.,von Borstel, A.,Chevour, P.,Awad, W.,Howson, L.J.,Littler, D.R.,Gherardin, N.A.,Le Nours, J.,Giles, E.M.,Berry, R.,Godfrey, D.I.,Davey, M.S.,Rossjohn, J.,Gully, B.S.
Recognition of the antigen-presenting molecule MR1 by a V delta 3 + gamma delta T cell receptor.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Unlike conventional αβ T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)δ1 and Vδ2 γδ TCR-mediated ligand recognition, the mode of Vδ3 TCR ligand engagement is unknown. MHC class I-related protein, MR1, presents vitamin B metabolites to αβ T cells known as mucosal-associated invariant T cells, diverse MR1-restricted T cells, and a subset of human γδ T cells. Here, we identify Vδ1/2 γδ T cells in the blood and duodenal biopsy specimens of children that showed metabolite-independent binding of MR1 tetramers. Characterization of one Vδ3Vγ8 TCR clone showed MR1 reactivity was independent of the presented antigen. Determination of two Vδ3Vγ8 TCR-MR1-antigen complex structures revealed a recognition mechanism by the Vδ3 TCR chain that mediated specific contacts to the side of the MR1 antigen-binding groove, representing a previously uncharacterized MR1 docking topology. The binding of the Vδ3 TCR to MR1 did not involve contacts with the presented antigen, providing a basis for understanding its inherent MR1 autoreactivity. We provide molecular insight into antigen-independent recognition of MR1 by a Vδ3 γδ TCR that strengthens an emerging paradigm of antibody-like ligand engagement by γδ TCRs.

PubMed: 34845016
DOI: 10.1073/pnas.2110288118

Experimental method

X-RAY DIFFRACTION (3.2 Å)