Chemical insights and new antigens for MAIT cell activation — ASN Events
  1. Schedule
  2. Poster Session 2 - Even Numbers + Rapid Fire 2 Posters
  3. Chemical insights and new antigens for MAIT cell activation

Chemical insights and new antigens for MAIT cell activation (#100)

Jeffrey YW Mak 1 2 , Weijun Xu 1 2 , Robert C Reid 1 2 , Alexandra J Corbett 3 , Bronwyn S. Meehan 3 , Huimeng Wang 3 , Zhenjun Chen 3 , Jamie Rossjohn 4 5 6 , James McCluskey 3 , Ligong Liu 1 2 , David P Fairlie 1 2
  1. ARC Centre of Excellence in Advanced Molecular Imaging, Brisbane, Queensland, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia
  3. Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia
  4. Infection and Immunity Program & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
  5. ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Victoria, Australia
  6. Institute of Infection and Immunity, Cardiff University, Cardiff, United Kingdom

Mucosal associated invariant T cells are activated by chemically unstable antigens (e.g. 5-OP-RU and 5-OE-RU). Here we compare and rationalize antigen instability, and develop a superior preparation of antigens with vastly improved purity and stability compared to current preparations. Secondly, we have created a functionally equivalent analogue of 5-OP-RU that is completely stable in water. Its MAIT cell activation potency correlates with its computationally predicted conformation. This analogue upregulates surface expression of human MR1, enables MR1 refolding to form MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. The analogue can also induce MAIT cell accumulation in mice lungs after administration with a co-stimulant. These antigens are useful for in vitro and in vivo MAIT cell studies, and their chemical and biological properties will be described.

  1. Mak, J. Y. W. et al. Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells. Nat. Commun. 8, 14599