bims-maitce Biomed News
on MAIT cells
Issue of 2026–04–05
two papers selected by
Andy E. Hogan, Maynooth University
  1. Restoration of Mucosa-Associated Invariant T-Cell Function in Healthcare-Associated Bacterial Infections Supports Recovery of Carbapenem Efficacy Against Resistant Bacteria Ex Vivo.
  2. Specific targeting of MR1-antigen complexes using nanobodies.
  1. J Infect Dis. 2026 Apr 02. pii: jiag151. [Epub ahead of print]
    Restoration of Mucosa-Associated Invariant T-Cell Function in Healthcare-Associated Bacterial Infections Supports Recovery of Carbapenem Efficacy Against Resistant Bacteria Ex Vivo.
    Yiting Xue, Asad Mustafa Karim, Wan Rong Sia, Fei Han, Kai Lin Chan, Nathalie Grace Chua, Leila Hadadi, Zhenyu Liu, Jeffrey Y W Mak, David P Fairlie, Lin-Fa Wang, Johan K Sandberg, Andrea Lay-Hoon Kwa, Edwin Leeansyah.
       BACKGROUND: Antimicrobial resistance (AMR) is a major challenge in healthcare-associated infections (HAIs), especially in immunocompromised individuals and those with comorbidities, who often have an impaired mucosa-associated invariant T (MAIT) cell pool. MAIT cells are innate-like T cells enriched in mucosal tissues with potent antimicrobial activity. Restoring their function may offer a host-directed strategy against drug-resistant pathogens.
    METHODS: We evaluated how cognate antigen in combination with cytokines modulates MAIT cell cytotoxicity and enhances carbapenem activity. MAIT cell cytolytic protein expression, cytotoxicity, and effector function were measured after stimulation. Secretomes from activated MAIT cells were tested against engineered Escherichia coli expressing clinically relevant carbapenemases.
    RESULTS: Under optimal conditions, MAIT cells upregulated antimicrobial cytolytic proteins and efficiently killed antigen-pulsed target cells. Interleukin (IL)-15 or IL-2 plus IL-7 most effectively promoted polyfunctional cytotoxic responses. Secretomes from cytokine-stimulated MAIT cells restored imipenem activity against Escherichia coli expressing blaNDM-1, blaKPC-2, and blaOXA-48, reducing metabolic activity, viability, and growth. Notably, IL-2 plus IL-7 enabled expansion and functional restoration of MAIT cells from HAI patients with diminished baseline numbers and responses.
    CONCLUSIONS: Tailored antigen and cytokine stimulation reinvigorates MAIT cell effector function and augments carbapenem efficacy, supporting MAIT cell-based host-directed adjunct strategies against AMR in vulnerable patients.
    Keywords:  anti-infectives; antimicrobial resistance; cytolytic proteins; healthcare-associated infections; mucosal-associated invariant T (MAIT) cells
    DOI:  https://doi.org/10.1093/infdis/jiag151
  2. bioRxiv. 2026 Mar 25. pii: 2026.03.22.713551. [Epub ahead of print]
    Specific targeting of MR1-antigen complexes using nanobodies.
    M H Shakir Hussain, Samuel J Redmond, Wael Awad, Calvin Xu, Caroline Soliman, Lisa Ciacchi, Alexis P Gonzalez, Jeffrey Y W Mak, David P Fairlie, James McCluskey, Adam P Uldrich, Jamie Rossjohn, Dale I Godfrey, Hui-Fern Koay, Nicholas A Gherardin.
      T cell receptor mimic (TCRm) antibodies and nanobodies that specifically bind peptide-HLA complexes have great therapeutic potential, as they can target polymorphic HLA on tumour cells furnishing peptides derived from tumour-associated antigens. MR1 is an MHC class-I-like molecule that exhibits limited polymorphism that binds and presents conserved metabolites, such as 5-OP-RU, derived from microbial riboflavin biosynthesis. Whether antibodies targeting such MR1-5-OP-RU complexes can be generated remains unclear. Using yeast display technology and in vitro affinity maturation, a nanobody with high affinity and fine specificity toward MR1-5-OP-RU complex was generated. These nanobodies bind both mouse and human MR1-5-OP-RU and inhibited MAIT cell responses to 5-OP-RU in vitro and in vivo demonstrating therapeutic potential. Moreover, we provide a molecular basis underpinning the fine specificity of these nanobodies, solving the crystal structures of MR1 in complex with either 5-OP-RU or Ac-6-FP. Here, the nanobody co-bound MR1 and 5-OP-RU, akin to a TCRm antibody. Moreover, we engineer bispecific antibodies targeting both MR1-5-OP-RU and CD3, that drive broad T cell killing of bacterially-infected cells as well as tumour cells treated with 5-OP-RU, thereby providing proof-of-principle for targeting the MR1 molecule with with TCRm-based nanobodies.
    One Sentence Summary: We report the development of a nanobody targeting MR1-5-OP-RU complex and demonstrate its utility to modulate MAIT cells responses, and as a bispecific engager.
    DOI:  https://doi.org/10.64898/2026.03.22.713551
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