Invariant V 7.2-J 33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells

Péterfalvi, Ágnes; Gömöri, Éva; Magyarlaki, T.; Pál, József; Bánáti, Miklós; Javorhazy, Andras; Szekeres-Barthó, Júlia; Szereday, László; Illés, Zsolt

doi:10.1093/intimm/dxn111

Cited by 84 publications

(63 citation statements)

References 37 publications

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“…Indeed, MAIT cells were present in several inflammatory tissues, such as multiple sclerosis neurologic lesions 37,38 or solid cancers. 15 The significance of these findings is difficult to assess in the absence of comparative analysis of blood and tissue MAIT cell numbers in several pathologic groups with similar inflammatory lesions, or without a functional analysis. On similar grounds, the significance of the high numbers of MAIT cells found in hepatitis C-infected livers becomes complex to assess because we show that they have a specific tropism for this organ.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] The frequency of these cells varies in certain pathologic conditions, such as cancer and viral or autoimmune diseases. [12][13][14][15] Recently, it has been demonstrated that a subset of naive cord blood CD4 T cells express CD161 and are precursors of peripheral, mature, Th17 T cells. 16 CD161 expression seems to correlate with interleukin-17 (IL-17) secretion by CD4 T cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

Dusséaux

Martin

Serriari

et al. 2011

Blood

846

1,333

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Mucosal-associated invariant T (MAIT) cells IntroductionMainstream T cells display a very diverse repertoire of antigen receptors, which enable these cells to respond to a wide variety of antigens presented by polymorphic major histocompatibility complex (MHC) molecules. During development, interactions between the T cells and selecting MHC class II and I molecules on thymic epithelial cells lead to the specific features of CD4 and CD8 T-cell lineage. However, 2 "innate-like" T lymphocytes, the natural killer T (NKT) and mucosal-associated invariant T (MAIT) cells, follow different ontogenic pathways with selection by nonpolymorphic MHC class Ib molecules. 1 Human MAIT cells express the semi-invariant T-cell receptor (TCR; iV␣7.2-J␣33) and are selected by the MHC class Ib molecule, MR1 on hematopoietic cells, which confer peculiar features. 2,3 Indeed, MAIT cells are enriched in the intestinal lamina propria and are numerous in the peripheral blood of healthy subjects. They are present in cord blood in small numbers with a naive phenotype, whereas in adults they represent approximately 10% of mature CD8 or CD4 Ϫ CD8 Ϫ (DN) T cells and display an effector-memory phenotype. We recently showed that MAIT cells specifically react against antigen-presenting cells (APCs), fed with a wide variety of bacteria and yeasts but not viruses, and display protective activity in experimental bacterial infection models. 4,5 In humans, they are defined as CD161 hi IL-18R␣ ϩ V␣7.2 ϩ ␥␦ Ϫ CD3 ϩ lymphocytes. 3,4 Either CD161 or IL-18R␣ expression at the cell surface, together with the V␣7.2 segment, allows for the unequivocal identification of MAIT cells in both peripheral blood and tissues. 3,4 CD161 (KLRB1, NKRP1A) is a C-type lectin family member, part of the NK complex. 6 Ligands for CD161 have been described only recently, and blocking or cross-linking CD161 may modulate T-cell functions. 7-9 CD161 is also expressed by the majority of NK cells and diverse subsets of T lymphocytes that include TCR-␥␦ T cells and most NKT cells. CD161 expression is found on a significant proportion of tissue-infiltrating T cells, such as the intestine and liver. [10][11][12] The frequency of these cells varies in certain pathologic conditions, such as cancer and viral or autoimmune diseases. [12][13][14][15] Recently, it has been demonstrated that a subset of naive cord blood CD4 T cells express CD161 and are precursors of peripheral, mature, Th17 T cells. 16 CD161 expression seems to correlate with interleukin-17 (IL-17) secretion by CD4 T cells. 17 Among TCR-␣␤ T cells, most of the CD161 ϩ T cells belong to the CD4 subset. However, CD8 T cells expressing CD161 can also be found, but their nature has just begun to be explored. CD161 ϩ CD8 T cells can be split into 2 different populations expressing intermediate or high levels of CD161. Two recent reports independently raised new findings on this latter subset. The first shows that CD161 hi CD8 T cells represent self-renewing memory cells, which survive chemotherapy. 18 These cells are absent from...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

Dusséaux

Martin

Serriari

et al. 2011

Blood

846

1,333

View full text Add to dashboard Cite

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“…The broad conservation of MAIT cells in mammals, restriction to an equally highly conserved MHC molecule, and their prevalence in barrier, mucosal tissues suggests that MAIT cell microbial detection has been an adaptation widely used in mammalian host defense. In addition to microbial detection, MAIT cells have been shown to demonstrate microbial-independent autoreactivity when MR1 is expressed at high levels on antigen-presenting cells, which may provide a link to MAIT cell involvement in autoimmune disorders and tumor immunosurveillance (11,12,25). This microbial-independent reactivity of MAIT cells is further enhanced by modification of a single amino acid residue, position 151 on the α2 helix.…”

Section: Discussionmentioning

confidence: 99%

The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins

López‐Sagaseta¹,

Dulberger²,

Crooks

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

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Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved αβ T-cell lineage that express a semi-invariant T-cell receptor (TCR) restricted to the MHC related-1 (MR1) protein. MAIT cells are dependent upon MR1 expression and exposure to microbes for their development and stimulation, yet these cells can exhibit microbial-independent stimulation when responding to MR1 from different species. We have used this microbial-independent, crossspecies reactivity of MAIT cells to define the molecular basis of MAIT-TCR/MR1 engagement and present here a 2.85 Å complex structure of a human MAIT-TCR bound to bovine MR1. The MR1 binding groove is similar in backbone structure to classical peptide-presenting MHC class I molecules (MHCp), yet is partially occluded by large aromatic residues that form cavities suitable for small ligand presentation. The docking of the MAIT-TCR on MR1 is perpendicular to the MR1 surface and straddles the MR1 α1 and α2 helices, similar to classical αβ TCR engagement of MHCp. However, the MAIT-TCR contacts are dominated by the α-chain, focused on the MR1 α2 helix. TCR β-chain contacts are mostly through the variable CDR3β loop that is positioned proximal to the CDR3α loop directly over the MR1 open groove. 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. Importantly, this structure also provides a critical link in our understanding of the evolution of αβ T-cell recognition of MHC and MHC-like ligands.M ucosal-associated invariant T (MAIT) cells are a highly conserved T-cell subset found in most mammalian species (1-4). In humans, they can constitute up to 10% of circulating double-negative T cells, although they are much less frequent in mice (1,5,6). Most MAIT cells lack expression of the CD4 or CD8 coreceptors, although many MAIT cells express the αα form of the CD8 coreceptor (1). In humans, these cells are found at moderate frequency in the intestine and represent up to ∼50% of T cells in the liver (7). The cells exhibit an effector-memory phenotype and express the CD161 receptor (6). Their presence as mature effector cells in the periphery is dependent on B cells and the gut commensal flora (6, 8). Stimulated human MAIT cells can express both proinflammatory cytokines (IFN-γ, TNF-α, and IL-17) and cytolytic effectors (granzyme B) (7, 9, 10). MAIT cells are known best for their reactivity against various microorganisms from both bacterial and fungal origin (9, 10). These microorganisms include several important human pathogens, such as Mycobacterium tuberculosis, Salmonella typhimurium, and Staphylococcus aureus. Indeed, a significant proportion of the nonclassically restricted responding T cells in M. tuberculosisinfected individuals were determined to be of the MAIT lineage (9). MAIT cells have also demonstrated autoreactivity and have been associated with various autoimmune disorders (11, 12); they have also been found in both k...

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“…In humans, MAIT cells were first reported in inflammatory lesions in MS, chronic inflammatory demyelinating polyneuropathy47 and neurological tumours48 using PCR for the canonical V α 7.2 − J α 33 TCR. It will be important to verify the specificity of these cells because non‐MAIT cells can express V α 7.2.…”

Section: Observations From Specific Diseasesmentioning

confidence: 99%

Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

2016

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SummaryMucosal‐associated invariant T (MAIT) cells are a novel class of innate‐like T cells, expressing a semi‐invariant T‐cell receptor (TCR) and able to recognize small molecules presented on the non‐polymorphic MHC‐related protein 1. Their intrinsic effector‐memory phenotype, enabling secretion of pro‐inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune‐mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation‐induced down‐regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR‐independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers.

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Invariant V 7.2-J 33 TCR is expressed in human kidney and brain tumors indicating infiltration by mucosal-associated invariant T (MAIT) cells

Cited by 84 publications

References 37 publications

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T cells

The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins

Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

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