4PJI

Structure of human MR1-Ac-6-FP in complex with human MAIT C-C10 TCR

Summary for 4PJI

• Entry DOI: 10.2210/pdb4pji/pdb
• Related: 4L4T 4NQC 4PJ5 4PJ7 4PJ8 4PJ9 4PJA 4PJB 4PJC 4PJD 4PJE 4PJF 4PJG 4PJH 4PJX
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, TCR-alpha, ... (8 entities in total)
• Functional Keywords: mr1, tcr, immune complex, ac-6-fp, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Single-pass membrane protein; Extracellular side. Isoform 4: Secreted. Isoform 3: Cell membrane; Single-pass type I membrane protein: Q95460; Secreted: P61769
• Total number of polymer chains: 8
• Total formula weight: 188681.44

Authors

Birkinshaw, R.W.,Rossjohn, J. (deposition date: 2014-05-12, release date: 2014-07-02, Last modification date: 2024-10-30)

Primary citation

Eckle, S.B.,Birkinshaw, R.W.,Kostenko, L.,Corbett, A.J.,McWilliam, H.E.,Reantragoon, R.,Chen, Z.,Gherardin, N.A.,Beddoe, T.,Liu, L.,Patel, O.,Meehan, B.,Fairlie, D.P.,Villadangos, J.A.,Godfrey, D.I.,Kjer-Nielsen, L.,McCluskey, J.,Rossjohn, J.
A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.
J.Exp.Med., 211:1585-1600, 2014

PubMed Abstract: Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR β-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) 3β loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3β 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.

PubMed: 25049336
DOI: 10.1084/jem.20140484

Experimental method

X-RAY DIFFRACTION (2.5 Å)