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Endoplasmic Reticulum Chaperones Stabilize Ligand-Receptive MR1 molecules for Efficient Presentation of Metabolite Antigens

ABSTRACT: Quantitative MS analysis of MR1 GFP immunoprecipates to identify steady-state binding partnets.

INSTRUMENT(S): impact II

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hela Cell

SUBMITTER: Laura Dagley

LAB HEAD: Hamish E.G. McWilliam

PROVIDER: PXD014585 | Pride | 2020-09-16

REPOSITORIES: Pride

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	P3197_CTRL_1_1_1_1_01_4822.d.zip	Other
	P3197_CTRL_1_2_1_1_01_4823.d.zip	Other
	P3197_CTRL_1_3_1_1_01_4824.d.zip	Other
	P3197_NL_1_1_1_1_01_4826.d.zip	Other
	P3197_NL_1_2_1_1_01_4827.d.zip	Other

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Publications

Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens.

McWilliam Hamish E G HEG Mak Jeffrey Y W JYW Awad Wael W Zorkau Matthew M Cruz-Gomez Sebastian S Lim Hui Jing HJ Yan Yuting Y Wormald Sam S Dagley Laura F LF Eckle Sidonia B G SBG Corbett Alexandra J AJ Liu Haiyin H Li Shihan S Reddiex Scott J J SJJ Mintern Justine D JD Liu Ligong L McCluskey James J Rossjohn Jamie J Fairlie David P DP Villadangos Jose A JA

Proceedings of the National Academy of Sciences of the United States of America 20200921 40

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B<sub>2</sub> synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled stable MR1 antigen analog, a conformation-specific MR1 mAb, proteomic ...[more]

PMID: 32958637

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PROTEOMIC ANALYSIS OF EXTRACELLULAR VESICLES FROM RHEUMATOID ARTHRITIS SYNOVIAL FLUID

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scRNA-sequencing of non-neuron cells from hippocampus (HP) of 7 months old Mr1+/+ and Mr1-/- mice.

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Transcriptome analysis of MR1 reactive T cells

Project description:MHC class I-related molecule MR1 presents riboflavin-derived microbial metabolites and folate-derivatives to mucosal-associated invariant T cells, but it is unknown whether MR1 can bind alternative antigens that stimulate other T cell lineages. Here we report that human T cells displaying diverse TCR-α and β chains recognize MR1-expressing cells in the absence of microbial ligands and respond to recombinant MR1 molecules loaded with antigens extracted from stimulatory targets. Transcriptome analysis revealed functional heterogeneity of MR1-reactive T cells (MR1T cells), which displayed differential expression of various transcription factors regulating T cell polarization, proliferation and apoptosis. Accordingly, MR1T cells displayed multiple profiles of chemokine receptor expression and secreted variable combinations of cytokines and growth factors, suggesting a diversity of immunological roles across numerous tissues. Functionally, MR1T cells were capable of inducing dendritic cell maturation and stimulating anti-microbial responses in intestinal epithelial cells. These data demonstrate that MR1 presents endogenous antigens to a novel population of functionally diverse human T cells.

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Nucleobase adducts bind MR1 and stimulate MR1-restricted T cells

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Single cell RNA-seq of metabolite specific T-cells (MR1-restricted) from adult mouse thymus

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