Bacteria, mucosal‐associated invariant T cells and MR1

Chua, Wei-Jen; Hansen, Ted H.

doi:10.1038/icb.2010.104

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…Although MAIT cells are known to respond to Gram-positive bacteria, Gram-negative bacteria and yeasts 5,6 , and have antimicrobial potential [7][8][9][10] , there is no consensus on their physiological role. Antigen recognition by MAIT cells is mediated by an ab T-cell receptor (TCR), in which the TCRVa chain comprises an almost-invariant Va7.2-Ja33 (TRAV1-2-TRAJ33) rearrangement paired with a limited number of TCRVb chains 1 .…”

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confidence: 99%

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

et al. 2014

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Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize conserved bacterial antigens derived from riboflavin precursors, presented by the nonpolymorphic MHC class I-like molecule MR1. Here we show that human MAIT cells are remarkably oligoclonal in both the blood and liver, display high inter-individual homology and exhibit a restricted length CDR3b domain of the TCRVb chain. We extend this analysis to a second sub-population of MAIT cells expressing a semi-invariant TCR conserved between individuals. Similar to 'conventional' MAIT cells, these lymphocytes react to riboflavin-synthesizing microbes in an MR1-restricted manner and infiltrate solid tissues. Both MAIT cell types release Th0, Th1 and Th2 cytokines, and sCD40L in response to bacterial infection, show cytotoxic capacity against infected cells and promote killing of intracellular bacteria, thus suggesting important protective and immunoregulatory functions of these lymphocytes.

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confidence: 99%

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

et al. 2014

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“…In these experiments, B-LCL cells were infected with E. coli strain BL21, treated or not (none) with mAbs to MR1 antigens (clone 26.5, 10 μg/ml) or IgG2 isotype control for 2 h and then exposed to MAIT cells. Because previous work has shown the ability of fixed targets to activated MAIT cells (6, 7, 44), we also compare frequency of IFN-γ + MAIT cells exposed to live infected targets or infected targets fixed in 1% paraformaldehyde. Although infected targets fixed in 1% paraformaldehyde were able to trigger an increase in the levels of IFN-γ + MAIT cells as compared to controls (uninfected targets), levels of IFN-γ + MAIT cells exposed to fixed targets were substantially lower than MAIT cells exposed to live infected targets (Figure 5A).…”

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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“…Consistent with this explanation, V␣19-J␣33 TCR-transgenic mice that overexpress MAIT cells had lower bacterial loads than control mice after infection with E. coli or M. abscessus (50). However, because the TCR-transgenic mice used in these comparisons have few if any conventional CD4 ϩ and CD8 ϩ T cells, this model system lacks physiologic context or the ability to address the question of whether MAIT cells have a nonredundant role in controlling bacterial infection (12). Another possible explanation to the inconsistency between in vivo and in vitro studies is that perhaps an infection model in mucosal tissues, where MAIT cells mainly reside, needs to be employed.…”

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confidence: 85%

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

et al. 2012

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ABSTRACTMucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Usingin vitroassays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth ofMycobacterium bovisBCG in macrophages (MΦ) 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. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection.

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Bacteria, mucosal‐associated invariant T cells and MR1

Cited by 10 publications

References 15 publications

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

B Cells Modulate Mucosal Associated Invariant T Cell Immune Responses

Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection

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