The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant alpha-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Valpha14 TCRalpha chain have been implicated in microbial and tumour responses, as well as in auto-immunity. Here we show that T cells that express the canonical hValpha7.2-Jalpha33 or mValpha19-Jalpha33 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. Selection and/or expansion of this population requires B lymphocytes, as MAIT cells are absent in B-cell-deficient patients and mice. In addition, we show that MAIT cells are selected and/or restricted by MR1, a monomorphic major histocompatibility complex class I-related molecule that is markedly conserved in diverse mammalian species. MAIT cells are not present in germ-free mice, indicating that commensal flora is required for their expansion in the gut lamina propria. This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity.

Conventional major histocompatibility complex (MHC) class I genes encode molecules that present intracellular peptide antigens to T cells. They are ubiquitously expressed and regulated by interferon y. Two highly divergent human MHC class I genes, MICA and MICB, are regulated by promoter heat shock elements similar to those ofHSP70 genes. MICA encodes a cell surface glycoprotein, which is not associated with f82-microglobulin, is conformationally stable independent of conventional class I peptide ligands, and almost exclusively expressed in gastrointestinal epithelium. Thus, this MHC class I molecule may function as an indicator of cell stress and may be recognized by a subset of gut mucosal T cells in an unusual interaction. tant cell lines, as well as in immunohistology stainings. The results show that MICA is a.highly glycosylated membraneanchored cell surface protein that is not associated with ,32mand is conformationally stable in the absence of conventional MHC class I peptide ligands. In accord with previous concepts, the almost exclusive expression of MICA in gastrointestinal epithelium combined with the intriguing transcriptional regulation of the MICA gene by a promoter heat shock element implies that this MHC class I molecule may function as a ligand for a subset of T cells in the intestinal intraepithelial lymphocyte compartment. This putative interaction is probably unrelated to conventional MHC class I antigen presentation and may serve a specialized T-cell immune surveillance function.Major histocompatibility complex (MHC) class I molecules are ubiquitously expressed heterodimers of a class I heavy chain and 132-microglobulin (f32m), which display peptides derived from proteins degraded in the cytosol on the cell surface and thus facilitate the recognition of intracellular antigens by circulating cytotoxic CD8+ T cells with ac3 T-cell receptors (1, 2). Class I related molecules have variously altered functions, including the presentation of lipid and lipoglycan compounds to CD4-8-T cells by human CDlb encoded outside the MHC (3, 4). Moreover, so-called nonclassical MHC class I molecules in the mouse selectively present bacterial peptides (5, 6), are recognized by T cells with y6 T-cell receptors in the absence of detectable bound peptides (7-10), or are mainly expressed in intestinal epithelium where they may interact with a subset of the resident T cells (11,12). Although the precise functions of some of these molecules remain to be defined, they are conceptually appreciated as potential components of a firstline immune defense (13,14). However, functionally corresponding genes and molecules have not been found in other mammals and humans. Conversely, two highly divergent human MHC class I genes closely linked to HLA-B, MICA, and MICB are conserved in most if not all mammals but seem to be missing in the mouse (15,16). These genes are transcribed in epithelial cell lines but not in B cells, T cells, and monocytes and are not induced by interferon y. Their translation products share an exc...

Major sctibit complex (MHC)

Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).