Atypical TRAV1-2- T cell receptor recognition of the antigen-presenting molecule MR1

Wael Awad, Erin W. Meermeier, Maria L. Sandoval-Romero, Jerome Le Nours, Aneta H. Worley, Megan D. Null, Ligong Liu, James McCluskey, David P. Fairlie, David M. Lewinsohn, Jamie Rossjohn

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2 Citations (Scopus)

Abstract

MR1 presents vitamin B-related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2+ αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2- MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2- TCRs interact with MR1-antigen complexes remains unclear. Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognizes an MR1-antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F'-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F'-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A'-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.

Original languageEnglish
Pages (from-to)14445-14457
Number of pages13
JournalJournal of Biological Chemistry
Volume295
Issue number42
DOIs
Publication statusPublished - 16 Oct 2020

Keywords

  • Antigen presentation
  • atypical MAIT TCR
  • crystal structure
  • immunology
  • MAIT
  • major histocompatibility complex (MHC)
  • MHC-related molecule (MR1)
  • protein structure
  • receptor structure-function
  • T-cell receptor (TCR)

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