bims-maitce Biomed News
on MAIT cells
Issue of 2026–04–19
three papers selected by
Andy E. Hogan, Maynooth University
  1. Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens.
  2. Universal Nanovial Screening Enables Functional Discovery of Metabolite-Reactive T-Cell Receptors for Cancer Therapy.
  3. MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells.
  1. Elife. 2026 Apr 14. pii: RP108318. [Epub ahead of print]14
    Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens.
    Se-Jin Kim, Jessie C Peterson, Andrew J Olive, Fikadu G Tafesse, Corinna A Kulicke, Elham Karamooz, David Lewinsohn.
      Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can be sensed by T cells, which are essential for the control of infection. In comparison to viral infections, Mtb antigens are relatively limited and hence, challenging to sample. Specialized antigen presentation pathways enable the presentation of such scarce antigens to CD8+ T cells, which are, thus, uniquely poised to survey intracellular environments. A subset of CD8+ T cells prevalent in the airways, known as mucosal-associated invariant T (MAIT) cells, can be activated through the presentation of Mtb antigens via the major histocompatibility complex class I-related protein 1 (MR1) molecule. Prior work demonstrates that endosomal calcium signaling is critical for MR1-mediated presentation of Mtb-derived antigens. Here, we show that the calcium-sensing trafficking proteins Synaptotagmin (Syt) 1 and Syt7 specifically promote MAIT cell activation in response to Mtb-infected cells. In bronchial epithelial cells, Syt1 and Syt7 localize to late endo-lysosomes and MR1 vesicles. Loss of Syt1 and Syt7 results in enlarged MR1 vesicles and an increased number of MR1 vesicles in close proximity to Mtb-containing vacuoles during infection. This study identifies a specialized pathway in which Syt1 and Syt7 facilitate the translocation of MR1 from Mtb-containing vacuoles, potentially to the cell surface for antigen presentation.
    Keywords:  bronchial epithelial cells; human; human cell lines; immunology; infectious disease; inflammation; microbiology; monocytic cells
    DOI:  https://doi.org/10.7554/eLife.108318
  2. ACS Nano. 2026 Apr 16.
    Universal Nanovial Screening Enables Functional Discovery of Metabolite-Reactive T-Cell Receptors for Cancer Therapy.
    Citradewi Soemardy, Yan-Ruide Li, Yichen Zhu, Xinyuan Shen, Lili Yang, Dino Di Carlo.
      Unconventional T cells, including mucosal-associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells, recognize nonpeptide antigens presented by MR1 and CD1d, respectively, and offer unique therapeutic potential. Despite invariant TCRα chains, diversity in TCRβ regions may underlie unique sequence-to-function relationships. Here, we develop a nanovial-based functional screening platform for the high-throughput discovery of TCRs from unconventional T cells present in human blood. By labeling nanovials with MR1 or CD1d molecules and cytokine-capture antibodies, we enable antigen-specific capture, activation, cytokine secretion, and oligobarcode-linked identification. Using secretion-encoded single-cell sequencing, we isolate rare MAIT and iNKT cells and associate their TCR identities with functional phenotypes. All five MAIT TCRs conferred antigen-specific cytokine secretion and cytotoxicity in vitro, with the two tested in vivo demonstrating tumor targeting, intratumoral accumulation, and measurable antitumor activity. Our nanotechnology-enabled "function-first" screen unlocks precision TCR discovery for unconventional T cells and supports the development of therapies targeting aberrant metabolic pathways.
    Keywords:  T-cell receptor (TCR) screening; cancer therapy; invariant natural killer T (iNKT) cell; mucosal-associated invariant T (MAIT) cell; nanovial; unconventional T cell
    DOI:  https://doi.org/10.1021/acsnano.5c22721
  3. Cell Mol Immunol. 2026 Apr 14.
    MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells.
    Sicheng Fu, Maoyu Tang, Changfeng Zhao, Sanwei Chen, Miya Su, Jun Pan, Yuwei Zhang, Xiaohu Wang, Wenhao Jia, Xinmin Chu, Shi Chen, Yusheng Chen, Lijian Chen, Tengchuan Jin, Zhigang Tian, Yubei Sun, Yeben Qian, Lianxin Liu, Hua Wang, Huimin Zhang, Li Bai.
      Mucosal-associated invariant T cells (MAITs) are enriched in the liver and closely related to human hepatocellular carcinoma (HCC), but their role is controversial. Whether and how the plasticity of MAITs modulates HCC progression remain to be explored. Here, we revealed that CD4+ MAITs displaying Th17 features were the major source of IL-17A in human HCC. IL-17A from Th17-polarized CD4+ MAITs promoted HCC progression by enhancing lipid storage and tumor cell proliferation in a PPARα dependent manner. Additionally, we showed that both TCR-dependent and TCR-independent activation signaling induced Th17-polarized CD4+ MAIT differentiation and that strong signaling promoted their differentiation. Moreover, IL-17A production in CD4+ MAITs was promoted by glycolysis via posttranscriptional regulation, and tumor cell-derived kynurenine enhanced glycolysis and IL-17A production through the AHR pathway. These findings demonstrate that the plasticity of MAITs and the generation of CD4+ MAITs promote HCC progression via metabolic crosstalk with tumor cells.
    Keywords:  CD4+ MAIT; Glycolysis; HCC; MAIT cell plasticity; Metabolic crosstalk; Th17 polarization
    DOI:  https://doi.org/10.1038/s41423-026-01409-8
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