PDBsum entry 4lcc

Immune system

PDB id: 4lcc

Contents

Protein chains

341 a.a.

157 a.a.

238 a.a.

Ligands

1XL

SO4 ×4

Waters ×1

PDB id:

4lcc

Name:

Immune system

Title:

Crystal structure of a human mait tcr in complex with a bacterial antigen bound to humanized bovine mr1

Structure:

Beta-2-microglobulin, mhc class i-related protein. Chain: c. Fragment: p01888 residues 21-118, c1itj8 residues 19-295. Engineered: yes. Mutation: yes. Other_details: fusion protein. Human mait tcr alpha chain. Chain: a. Engineered: yes.

Source:

Bos taurus. Bovine,cow,domestic cattle,domestic cow. Organism_taxid: 9913. Gene: mr1, bt.63045. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

3.26Å R-factor: 0.260 R-free: 0.312

Authors:

J.Lopez-Sagaseta,E.J.Adams

Key ref:

J.López-Sagaseta et al. (2013). MAIT recognition of a stimulatory bacterial antigen bound to MR1. J Immunol, 191, 5268-5277. PubMed id: 24108697 DOI: 10.4049/jimmunol.1301958

Date:

21-Jun-13 Release date: 16-Oct-13

Protein chain

C1ITJ8  (HMR1_BOVIN) -  Major histocompatibility complex class I-related gene protein from Bos taurus

Seq: 336 a.a.

Struc: 341 a.a.*

Protein chain

P01888  (B2MG_BOVIN) -  Beta-2-microglobulin from Bos taurus

Seq: 118 a.a.

Struc: 341 a.a.*

Protein chain

Q6P4G7  (Q6P4G7_HUMAN) -  TRA@ protein from Homo sapiens

Seq: 260 a.a.

Struc: 157 a.a.*

Protein chain

P01850  (TRBC1_HUMAN) -  T cell receptor beta constant 1 from Homo sapiens

Seq: 176 a.a.

Struc: 238 a.a.*

* PDB and UniProt seqs differ at 41 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1301958

J Immunol 191:5268-5277 (2013)

PubMed id: 24108697

MAIT recognition of a stimulatory bacterial antigen bound to MR1.

J.López-Sagaseta, C.L.Dulberger, A.McFedries, M.Cushman, A.Saghatelian, E.J.Adams.

ABSTRACT

MR1-restricted mucosal-associated invariant T (MAIT) cells represent a subpopulation of αβ T cells with innate-like properties and limited TCR diversity. MAIT cells are of interest because of their reactivity against bacterial and yeast species, suggesting that they play a role in defense against pathogenic microbes. Despite the advances in understanding MAIT cell biology, the molecular and structural basis behind their ability to detect MR1-Ag complexes is unclear. In this study, we present our structural and biochemical characterization of MAIT TCR engagement of MR1 presenting an Escherichia coli-derived stimulatory ligand, rRL-6-CH2OH, previously found in Salmonella typhimurium. We show a clear enhancement of MAIT TCR binding to MR1 due to the presentation of this ligand. Our structure of a MAIT TCR/MR1/rRL-6-CH2OH complex shows an evolutionarily conserved binding orientation, with a clear role for both the CDR3α and CDR3β loops in recognizing the rRL-6-CH2OH stimulatory ligand. We also present two additional xenoreactive MAIT TCR/MR1 complexes that recapitulate the docking orientation documented previously, despite having variation in the CDR2β and CDR3β loop sequences. Our data support a model by which MAIT TCRs engage MR1 in a conserved fashion, with their binding affinities modulated by the nature of the MR1-presented Ag or diversity introduced by alternate Vβ usage or CDR3β sequences.