Dataset Information

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

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.

SUBMITTER: Awad W

PROVIDER: S-EPMC7573270 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Awad Wael W Meermeier Erin W EW Sandoval-Romero Maria L ML Le Nours Jérôme J Worley Aneta H AH Null Megan D MD Liu Ligong L McCluskey James J Fairlie David P DP Lewinsohn David M DM Rossjohn Jamie J

The Journal of biological chemistry 20200814 42

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 D46 ...[more]

PMID: 32817339

Similar Datasets

Project description:BackgroundT cell receptors (TCRs) can recognize diverse lipid and metabolite antigens presented by MHC-like molecules CD1 and MR1, and the molecular basis of many of these interactions has not been determined. Here we applied our protein docking algorithm TCRFlexDock, previously developed to perform docking of TCRs to peptide-MHC (pMHC) molecules, to predict the binding of αβ and γδ TCRs to CD1 and MR1, starting with the structures of the unbound molecules.ResultsEvaluating against TCR-CD1d complexes with crystal structures, we achieved near-native structures in the top 20 models for two out of four cases, and an acceptable-rated prediction for a third case. We also predicted the structure of an interaction between a MAIT TCR and MR1-antigen that has not been structurally characterized, yielding a top-ranked model that agreed remarkably with a characterized TCR-MR1-antigen structure that has a nearly identical TCR α chain but a different β chain, highlighting the likely dominance of the conserved α chain in MR1-antigen recognition. Docking performance was improved by re-training our scoring function with a set of TCR-pMHC complexes, and for a case with an outlier binding mode, we found that alternative docking start positions improved predictive accuracy. We then performed unbound docking with two mycolyl-lipid specific TCRs that recognize lipid-bound CD1b, which represent a class of interactions that is not structurally characterized. Highly-ranked models of these complexes showed remarkable agreement between their binding topologies, as expected based on their shared germline sequences, while differences in residue-level interactions with their respective antigens point to possible mechanisms underlying their distinct specificities.ConclusionsTogether these results indicate that flexible docking simulations can provide accurate models and atomic-level insights into TCR recognition of MHC-like molecules presenting lipid and other small molecule antigens.

Dataset Information

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

Publications

Atypical TRAV1-2<sup>-</sup> T cell receptor recognition of the antigen-presenting molecule MR1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Publications

Atypical TRAV1-2&lt;sup&gt;-&lt;/sup&gt; T cell receptor recognition of the antigen-presenting molecule MR1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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

Atypical TRAV1-2<sup>-</sup> T cell receptor recognition of the antigen-presenting molecule MR1.