Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells*

  title={Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells*},
  author={Shouxiong Huang and Susan Gilfillan and Marina Cella and Michael J. Miley and Olivier Lantz and Lonnie Lybarger and Daved H. Fremont and Ted. H. Hansen},
  journal={Journal of Biological Chemistry},
  pages={21183 - 21193}
The novel class Ib molecule MR1 is highly conserved in mammals, particularly in its α1/α2 domains. Recent studies demonstrated that MR1 expression is required for development and expansion of a small population of T cells expressing an invariant T cell receptor (TCR) α chain called mucosal-associated invariant T (MAIT) cells. Despite these intriguing properties it has been difficult to determine whether MR1 expression and MAIT cell recognition is ligand-dependent. To address these outstanding… 

Figures from this paper

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries
The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer.
MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution
It is shown that both mouse and human MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination, demonstrating that the presentation pathway of MR1 toMAIT cells is highly evolutionarily conserved.
Mucosal‐associated invariant T cell receptor recognition of small molecules presented by MR1
The key molecular interactions underlying the recognition and reactivity of MAIT TCRs to MR1 are defined in an Ag‐dependent manner and this metabolite Ag‐presenting molecule was shown to trap chemical scaffolds including drug and drug‐like molecules.
Endogenous MHC-Related Protein 1 Is Transiently Expressed on the Plasma Membrane in a Conformation That Activates Mucosal-Associated Invariant T Cells
This article defines a unique mAb capable of stabilizing endogenous mouse MR1 at the cell surface, resulting in enhanced mouse MAIT cell activation and demonstrated that under basal conditions, endogenous MR1 transiently visits the cellsurface, thus reconciling the aforementioned serologic and functional studies.
MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells
It is demonstrated that MR1 antigen presentation is not affected by either the proteasome or the class I chaperones, and the class II chaperone invariant chain, Ii, physically associates with MR1 and promotes its endosomal trafficking.
Differential antigenic requirements by diverse MR1‐restricted T cells
MHC‐related protein 1 (MR1) presents microbial riboflavin metabolites to mucosal‐associated invariant T (MAIT) cells for surveillance of microbial presence and TCR gene transfer and engineered MR1‐expressing antigen‐presenting cells are used to probe the MR1 restriction and antigen reactivity of a range of MR 1‐restricted TCRs, including model tumor‐reactive T CRs.
Expression and trafficking of MR1
This paper proposes a model for the loading and trafficking of MR1, a non‐polymorphic MHC class IB antigen‐presenting molecule that is the restricting molecule for mucosal‐associated invariant T cells, a prominent population of innate‐like antibacterial T cells.
The Role of Mucosal Associated Invariant T Cells in Antimicrobial Immunity
Given that MAIT cells are pro-inflammatory, serve in early control of bacterial infections, and appear enriched at tissue sites where microbes interface and gain access to the body, it is postulate that they play an important role in antimicrobial immune responses.
Specific for Riboflavin Metabolites Mucosal-Associated Invariant T Cells Antimycobacterial Effects of Mouse Functional Heterogeneity and
It is demonstrated that MR1/ribityllumazine (RL) tetramer + mouse MAIT cells contain heterogeneous populations, as well as thatMR1 expression leads to the development of more “classic” MAIT cell populations (increased V b 6/8 + NK1.1 +MAIT cells that can be activated by either MR1-restricted TCR signaling or innate cytokine stimulation).
MAIT Cell Recognition of MR1 on Bacterially Infected and Uninfected Cells
Mucosal-associated invariant T cells are a unique population of T cells that express a semi-invariant αβ TCR and are restricted by the MHC class I-related molecule MR1. MAIT cells recognize


Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1
It is shown that T cells that express the canonical hVα7.2-Jα33 or mVα19-J α33 TCR rearrangement are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells.
The Recognition of the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule, T10, by the γδ T Cell, G8
It is shown that one of the H-2T region–encoded molecules, T10, when produced in Escherichia coli, can be folded in vitro with β2-microglobulin (β2m) to form a stable heterodimer in the absence of peptide or nonpeptide moieties.
Definition and transfer of a serological epitope specific for peptide-empty forms of MHC class I.
This work shows that mAb 64-3-7 detects a linear stretch of amino acids including principally residues 48Q and 50P and demonstrates that the 64- 3-7 epitope can be transferred to other class I molecules with limited mutagenesis.
A structural basis for immunodominant human T cell receptor recognition
The crystal structure of Vβ17Vα10.2 is determined and it is shown that, whereas the TCR typically fits over an exposed side chain of the peptide, in this structure MP(58–66) exposes only main chain atoms, which underlies the immunodominant T cell response.
Biochemical Features of the MHC-Related Protein 1 Consistent with an Immunological Function1
It is shown for the first time that both mouse and human MR1 molecules can associate with the peptide-loading complex and can be detected at low levels at the surface of transfected cells, demonstrating that surface expression of MR1 is possible but may be limited by a specific ligand or associated molecule.
Binding of peptides lacking consensus anchor residue alters H-2Ld serologic recognition.
Data imply that a mAb to a class I molecule can distinguish peptides with different motifs, possibly reflecting peptide-dependent conformational changes in the class I molecules.
The Majority of H2-M3 Is Retained Intracellularly in a Peptide-Receptive State and Traffics to the Cell Surface in the Presence of N-Formylated Peptides
We used a new monoclonal antibody (mAb 130) to analyze the intracellular trafficking and surface expression of H2-M3, the major histocompatibility complex class Ib molecule that presents N-formylated
Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene.
The molecular identity of all human and murine MR1 isoforms generated through a complex scenario of alternative splicing is defined, some encoding secretory variants lacking the Ig-like alpha3 domain, and ubiquitous transcription of these MR1 variants in several major cell lineages is shown.
Alloreactive and syngeneic CTL are comparably dependent on interaction with MHC class I alpha-helical residues.
It is unequivocally demonstrate that self-restricted and alloreactive T cells do not differ, but rather are comparably dependent on interaction with MHC residues.