4IIQ

Crystal structure of a human MAIT TCR in complex with bovine MR1

Summary for 4IIQ

• Entry DOI: 10.2210/pdb4iiq/pdb
• Descriptor: Human Mucosal Associated Invariant T cell receptor alpha chain, Human Mucosal Associated Invariant T cell receptor beta chain, Beta-2-microglobulin, MHC class I-related protein, ... (5 entities in total)
• Functional Keywords: mhc-class i, immunoglobulin domain, immune system, antigen presentation, antigen recognition, cell membrane
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01888
• Total number of polymer chains: 3
• Total formula weight: 96854.59

Authors

Lopez-Sagaseta, J.,Adams, E.J. (deposition date: 2012-12-20, release date: 2013-04-24, Last modification date: 2025-03-26)

Primary citation

Lopez-Sagaseta, J.,Dulberger, C.L.,Crooks, J.E.,Parks, C.D.,Luoma, A.M.,McFedries, A.,Van Rhijn, I.,Saghatelian, A.,Adams, E.J.
The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins.
Proc.Natl.Acad.Sci.USA, 110:E1771-E1778, 2013

PubMed Abstract: Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved αβ T-cell lineage that express a semi-invariant T-cell receptor (TCR) restricted to the MHC related-1 (MR1) protein. MAIT cells are dependent upon MR1 expression and exposure to microbes for their development and stimulation, yet these cells can exhibit microbial-independent stimulation when responding to MR1 from different species. We have used this microbial-independent, cross-species reactivity of MAIT cells to define the molecular basis of MAIT-TCR/MR1 engagement and present here a 2.85 Å complex structure of a human MAIT-TCR bound to bovine MR1. The MR1 binding groove is similar in backbone structure to classical peptide-presenting MHC class I molecules (MHCp), yet is partially occluded by large aromatic residues that form cavities suitable for small ligand presentation. The docking of the MAIT-TCR on MR1 is perpendicular to the MR1 surface and straddles the MR1 α1 and α2 helices, similar to classical αβ TCR engagement of MHCp. However, the MAIT-TCR contacts are dominated by the α-chain, focused on the MR1 α2 helix. TCR β-chain contacts are mostly through the variable CDR3β loop that is positioned proximal to the CDR3α loop directly over the MR1 open groove. The elucidation of the MAIT TCR/MR1 complex structure explains how the semi-invariant MAIT-TCR engages the nonpolymorphic MR1 protein, and sheds light onto ligand discrimination by this cell type. Importantly, this structure also provides a critical link in our understanding of the evolution of αβ T-cell recognition of MHC and MHC-like ligands.

PubMed: 23613577
DOI: 10.1073/pnas.1222678110

Experimental method

X-RAY DIFFRACTION (2.86 Å)