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Publication Abstract from PubMed

Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved alphabeta 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 A 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 alpha1 and alpha2 helices, similar to classical alphabeta TCR engagement of MHCp. However, the MAIT-TCR contacts are dominated by the alpha-chain, focused on the MR1 alpha2 helix. TCR beta-chain contacts are mostly through the variable CDR3beta loop that is positioned proximal to the CDR3alpha 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 alphabeta T-cell recognition of MHC and MHC-like ligands.

The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins.,Lopez-Sagaseta J, Dulberger CL, Crooks JE, Parks CD, Luoma AM, McFedries A, Van Rhijn I, Saghatelian A, Adams EJ Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1771-8. doi:, 10.1073/pnas.1222678110. Epub 2013 Apr 23. PMID:23613577^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.