MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution

  title={MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution},
  author={Shouxiong Huang and Emmanuel Martin and Sojung Kim and Lawrence Yu and Claire Soudais and Daved H. Fremont and Olivier Lantz and Ted. H. Hansen},
  journal={Proceedings of the National Academy of Sciences},
  pages={8290 - 8295}
Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel class Ib molecule with properties highly suggestive of its regulation of mucosal immunity. The Mr1 gene is evolutionarily conserved, is non-Mhc linked, and controls the development… 

Figures from this paper

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection
It is shown that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of Mycobacterium bovis BCG in macrophages in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ.
The Immune Modulating Properties of Mucosal-Associated Invariant T Cells
Understanding of the molecular mechanisms underpinning MAIT cell activation and effector function in health and disease will aid in clinically harnessing this unique, not donor-restricted cell subtype, according to its importance in tissue repair and control of immune homeostasis.
The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins
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, a critical link in the understanding of the evolution of αβ T-cell recognition of MHC and MHC-like ligands.
Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells
Mucosal‐associated invariant T (MAIT) cells are a subset of unconventional T cells restricted by the major histocompatibility complex (MHC) class I–like molecule MHC‐related protein 1 (MR1). MAIT
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.
MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection
In vivo evidence is provided demonstrating that MAIT cells are an important T-cell subset with activities that influence the innate and adaptive phases of mucosal immunity.
Bacteria, mucosal‐associated invariant T cells and MR1
Certain subpopulations of T lymphoctyes show innate-like properties that distinguish them from conventional T cells and thus have been collectively termed innate T cells, and it is attractive to propose that they represent ancient innate pathways of pathogen protection.


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.
Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells*
Monoclonal antibodies were produced in MR1 knock-out mice immunized with recombinant MR1 protein, and a series of MR1 mutations were generated at sites previously shown to disrupt the ability of class Ia molecules to bind peptide or TCR, supporting the conclusion that MR1 has an antigen presentation function.
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.
Stepwise Development of MAIT Cells in Mouse and Human
MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora.
MR1-Restricted Vα19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response1
Evidence is provided for what may be two functionally distinct MAIT cell populations, and the idea that MAIT cells contribute to the innate immune response in the gut mucosa is strongly supported.
The biology of NKT cells.
NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.
CTL responses to H2‐M3‐restricted Listeria epitopes
FMet peptide‐specific CTL responses are observed in a large proportion of cultures from non immunized, conventionally housed mice and may reflect priming in vivo on cross‐reactive antigens, or may indicate that requirements for priming of H2‐M3‐restricted CTL are less stringent than for class Ia‐restricted responses.
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.