Human MR1 expression on the cell surface is acid sensitive, proteasome independent and increases after culturing at 26 °C

Abós, Beatriz; Moral, Manuel Gómez del; Gozalbo-López, Beatriz; López-Relaño, Juan; Viana, Vanesa; Martı́nez-Naves, Eduardo

doi:10.1016/j.bbrc.2011.07.007

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…Like MHC class I and CD1d, MR1 associates directly and non‐covalently with β 2 m . Consistent with this, MR1 expression is not seen in Daudi cells, which lack β 2 m . Association of MR1 with β 2 m is required for trafficking of MR1 from the endoplasmic reticulum (ER) to the Golgi and is also required for surface expression .…”

Section: Intracellular Trafficking Of Mr1mentioning

confidence: 67%

“…The existence of non‐folic acid‐derived ligands is suggested by the detection of low levels of the folded form of MR1 at the cell surface in the absence of folic acid or an exogenous ligand . An endogenous ligand could covalently bind to MR1 Lys43 through the formation of a Schiff base, as reported for 6‐FP, or could bind non‐covalently to MR1 and neutralize Lys43, as reported for some ribityllumazines, diclofenac and 5′‐hydroxylated diclofenac . The existence of a non‐covalently bound ligand would be consistent with the observation that MR1 can be loaded at the cell surface; alternatively, surface loading may be explained by the surface expression of small amounts of unloaded, open conformation MR1, which has been reported in cells overexpressing MR1 …”

Section: Intracellular Trafficking Of Mr1mentioning

confidence: 97%

“…Several studies have assessed the expression of MR1 protein. Using anti‐MR1 antibody 26.5, which only recognizes MR1 in a folded (presumed to be ligand‐bound) form, surface expression of MR1 was seen at 37° on some (C1R, L721.221) but not all (JY) B‐cell‐derived cell lines, to a lesser degree on some (Jurkat and SupT1) but not all (Molt4, Peer) T‐cell lines, and was absent from myeloid (U937, HL‐60, K562, NB4) and epithelial cell lines (Caco2, T84) . Using antibody 12.2, which also only recognizes MR1 in a folded form, MR1 expression was seen on the L721.221 B‐cell line and Jurkat and SupT1 T‐cell lines, and at low levels on C1R and JY B‐cell lines .…”

Section: Mr1 Protein Expressionmentioning

confidence: 99%

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Expression and trafficking of MR1

Lamichhane

Ussher

2017

Immunology

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SummaryMHC class I-related gene protein (MR1) is a non-polymorphic MHC class IB antigen-presenting molecule that is the restricting molecule for mucosal-associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals. In humans and rodents it is expressed in a broad range of cell types, both haematopoietic and non-haematopoietic, although cell surface expression has been difficult to detect. Although MR1 trafficking shares features with both the MHC class I and MHC class II pathways, it is distinct. Several strands of evidence suggest that the intracellular location where MR1 is loaded differs for soluble ligand and for ligand derived from intact bacteria. The regulation of MR1 surface expression may also vary between different cell types. This paper will review what is currently known about the expression and trafficking of MR1 and propose a model for the loading and trafficking of MR1.

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Section: Intracellular Trafficking Of Mr1mentioning

confidence: 67%

Section: Intracellular Trafficking Of Mr1mentioning

confidence: 97%

Section: Mr1 Protein Expressionmentioning

confidence: 99%

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Expression and trafficking of MR1

Lamichhane

Ussher

2017

Immunology

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“…While B-LCL cells infected with BL21 and EPEC induced high levels of MR1 on the cell surface, B-LCL cells infected with E. coli strains HS and Nissle 1917, EIEC , and S. typhi induced only low levels of MR1 on the cell surface (Figures 2A,B). Because previous work has shown the presence of MR1 proteins intracellularly in different types of B and T cell lines (37), we speculated that MR1 proteins might have been exported to the cell surface from a pool of endogenous MR1 already present in the cytoplasm of target cells. Thus, B-LCL targets were either surface stained only (non-permeabilized cells) or surface and intracellular stained (total; permeabilized cells) with anti-MR1 antibodies.…”

Section: Resultsmentioning

confidence: 99%

B Cells Modulate Mucosal Associated Invariant T Cell Immune Responses

2014

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A common finding when measuring T cell immunity to enteric bacterial vaccines in humans is the presence of background responses among individuals before immunization. Yet the nature of these background responses remains largely unknown. Recent findings show the presence in uninfected individuals of mucosal associated invariant T (MAIT) cells that mount broad spectrum immune responses against a variety of microorganisms including Mycobacterium tuberculosis and enteric bacteria such as Escherichia coli and Salmonella. Therefore, we investigated whether MAIT immune responses to intestinal bacteria might account for the background responses observed before immunization. Here we measured MAIT immune responses to commensal and enteric pathogenic bacteria in healthy individuals with no history of oral immunization with enteric bacteria. We found that MAIT cells were activated by B cells infected with various bacteria strains (commensals and pathogens from the Enterobacteriaceae family), but not by uninfected cells. These responses were restricted by the non-classical MHC-related molecule 1 (MR1) and involved the endocytic pathway. The quality of these responses (i.e., cytokine profile) was dependent on bacterial load but not on the level expression of MR1 or bacterial antigen on B cell surface, suggesting that a threshold level of MR1 expression is required to trigger MAIT activation. These results provide important insights into the role of B cells as a source of antigen-presenting cells to MAIT cells and the gut immune surveillance of commensal microbiota.

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“…In line with earlier studies, Huang et al [62] demonstrated that MR1 traffics through endocytic compartments, thereby allowing MAIT cells to sample both endocytosed and endogenous antigens. Furthermore, the stability of MR1 at the cell surface is affected by external factors such as pH [63].…”

Section: Mr1 Expression Structure and Functionmentioning

confidence: 99%