Project description:Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8α co-receptor (CD8+), with a smaller subset lacking both CD4 and CD8 (DN). However, it is unclear if these two MAIT cell sub-populations distinguished by CD8α represent functionally distinct subsets. To address this, we investigated the phenotypic, transcriptional, and functional differences between CD8+ and DN MAIT cells using human samples from peripheral blood, mucosal tissues, and fetal tissues.
Project description:A recently identified unconventional T cell population known as mucosal-associated invariant T (MAIT) cells are characterized by the expression of semi-invariant T cell receptor (TCR) with a canonical TRAV1-2/TRAJ33 (Vα7.2/Jα33). These evolutionary conserved, innate-like T cells recognize vitamin B metabolites, derived from some bacteria and fungi. Due to their presence not only in the T cell repertoire of mucosal surfaces but also in peripheral blood and liver, and their significant involvement in a wide range of diseases, in-depth characterization of human MAIT cells is a timely requirement. Studies that examined the transcriptome, immunoproteome, and whole-cell proteome characterized the role of cytotoxic molecules and cytokines in effector functions of MAIT cells and their relationship with some other immune cell subsets. As MAIT cells are classified under the CD3+ T cell compartment and the majority express surface receptor CD8, identifying their proteomic relationship with CD3+ and CD8+ T cells is pivotal. Thus, a high-resolution dataset was generated using the cell populations sorted from peripheral blood mononuclear cells of three healthy volunteers to describe the whole cell proteomes of MAIT, CD3+, and CD8+ T cells. Trypsin-digested peptide samples obtained from the methanol co-precipitation method were analyzed using an Orbitrap FusionTM TribridTM mass spectrometer (Thermo Fisher Scientific, USA) inline coupled to nanoACQUITY ultra-performance liquid chromatography system (Waters, USA) to acquire data-dependent shotgun proteomic data (DDA-MS) for label-free quantification. Analysis of raw DDA-MS data using MaxQuant software and maxLFQ identified and quantified 4,442 protein groups at a 1% false discovery rate. Further analysis identified 3,680 proteins which were detected with a single UniProt accession and a minimum of 2 unique or razor peptides. Thus this proteomic dataset can be used as a reference proteome for future studies on human MAIT cells.
Project description:This SuperSeries is composed of the following subset Series: GSE33374: Expression data from healthy human CD161++CD8aa and CD161++CD8ab T cells GSE33424: Expression data from human cord blood CD161++/CD161+/CD161- CD8+ T cell subsets Refer to individual Series
Project description:We report the transcriptomic landscape of MAIT cell development by examining thymic immature stage 1 and mature stage 3 MAIT cells from mouse thymus, and thymic immature stage 1, stage 2 mature stage 3 MAIT cells from human thymus using RNAseq.
Project description:We report the transcriptomic landscape of MAIT cell development by examining thymic immature stage 1 and mature stage 3 MAIT cells from mouse thymus, and thymic immature stage 1, stage 2 mature stage 3 MAIT cells from human thymus using RNAseq.
Project description:In mice, contrary to conventional T cells, MAIT cells acquire a memory phenotype in the thymus in relation with Zbtb16 expression (Savage et al., 2008 ; Koay et al., 2016). To define phenotypic transcriptional signatures of MAIT subsets in the thymus, we analyzed by microarray the transcriptome of MAIT1 (MR1tet+RORgt+) and MAIT17 (MR1tet+RORgt+) as compared to conventional mature (TCRb+CD24lo) CD4+ and CD8+ single positive cells.
Project description:Mucosal associated invariant T (MAIT) cells, already differentiated and located at mucosal sites, are critical in the body’s first wave of defenses against invading pathogens. Bcl11b KO MAIT cells fail to be maintained both in the thymus and peripheral organs. Furthermore, MAIT cells fail to fully develop in the thymus without Bcl11b, failing to upregulate RORγt, and that phenotype remains in the lungs and livers of these mice. Bcl11b deletion in MAIT cells causes dramatic shifts in the activation and TH17 programs, due to the binding of Bcl11b in many of those genes, which we have seen in the human MAIT cells. MAIT cells rely on PLZF and RORγt for their development and function, while also heavily relying on Bcl11b. These data show the key interplay of Bcl11b with PLZF and RORγt in a T cell leading to its development and necessary function to protect the body against diseases.
Project description:Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses, which can augment early immune responses and contribute to protection from lethal infection. Thus, we reasoned MAIT cells may have an adjuvating role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel vaccine platforms for pandemic pathogens such as Ebola virus and SARS-CoV-2. In both mice and human volunteers, immunization with ChAdOx1 (Chimpanzee Adenovirus Ox1) robustly activated MAIT cells. Activation required transduction of plasmacytoid dendritic cells and monocytes to produce IFN- and IL-18, respectively. IFN--induced monocyte-derived TNF was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines both in vitro and in vivo. Strikingly, vaccine-induced activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers. Supporting a causal relationship, MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. These findings define a novel role for MAIT cells in the immunogenicity of adenovirus vector vaccines, with potential implications for vaccine design.