4PJA: Structure Of Human Mr1-5-op-ru In Complex With Human Mait B-b10 Tcr

Citation:
Abstract
Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) alpha-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR beta-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to structural alterations in MR1 that subsequently affected MAIT TCR recognition via conformational changes within the complementarity-determining region (CDR) 3beta loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3beta hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag-dependent manner, thereby modulating MAIT cell recognition.
PDB ID: 4PJADownload
MMDB ID: 121202
PDB Deposition Date: 2014/5/12
Updated in MMDB: 2014/08
Experimental Method:
x-ray diffraction
Resolution: 2.68  Å
Source Organism:
Similar Structures:
Biological Unit for 4PJA: tetrameric; determined by author
Molecular Components in 4PJA
Label Count Molecule
Proteins (4 molecules)
1
Major Histocompatibility Complex Class I-related Gene Protein(Gene symbol: MR1)
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
1
Tcr-alpha
Molecule annotation
1
Tcr-beta
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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