ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

A Vδ3+ subset of MR1 reactive γδ T cells recognise the side of the MR1 molecule (#265)

Michael T Rice 1 2 , Anouk von Borstel 2 , Priyanka Chevour 2 , Wael Awad 2 , Lauren J Howson 2 , Dene R Littler 2 , Nicholas A Gherardin 3 4 , Jérôme Le Nours 1 2 , Edward M Giles 5 , Richard Berry 1 2 , Dale I Godfrey 3 4 , Martin S Davey 1 2 , Jamie Rossjohn 1 2 6 , Benjamin S Gully 1 2
  1. Australian Research Council Centre of Excellence in Adavanced Molecular Imaging, Monash University, Clayton, Victoria, Australia
  2. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, 3800, Victoria, Australia
  3. Australian Research Council Centre of Excellence in Adavanced Molecular Imaging, University of Melbourne, Melbourne, Victoria, Australia
  4. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, 3000, Victoria , Australia
  5. Department of Paediatrics, Monash University and Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medicine, 27-31 Wright St, Clayton, 3168, Victoria, Australia
  6. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK

T cells are broadly categorised by their expression of either an αβ or γδ T cell receptor (TCR). Whilst αβ T cells are comprehensively understood γδ T cells are ill-defined but are increasingly realised to be an important T cell subset that display both innate- and adaptive-like immune functions. The breadth of antigens recognized by γδ T cells remains incomplete, although generally they recognize non-peptide ligands independent of the Major Histocompatibility Complex (MHC). To date, the antigen reactivity and effector functions of Vδ1 and Vδ2 γδ T cell subsets remain the best characterized, whilst Vδ3 T cells are predominately ignored. The MHC class 1 related protein (MR1), presents bacterial vitamin B metabolites to both αβ mucosal associated invariant T cells (MAIT) and γδ T cells (1). Here, we identify MR1 reactivity of Vδ1/2- T cells in donor matched blood and duodenal samples in children, with an enrichment of Vδ3 cells within the gut. Biochemical analysis of a Vδ3-Vγ8 TCR, revealed broad MR1 reactivity independent of the presented metabolite antigen, yet displayed vestiges of antigen modulated recognition. We then determined, to our knowledge, the first Vδ3 TCR-antigen complex structures. This revealed a novel docking topology, recognizing the side of the MR1 antigen presenting molecule making no contacts to the presented antigen. This is in stark contrast to previously characterized MAIT and γδ TCRs, which bind the top and underside of the MR1 antigen presenting groove, respectively. Ultimately, our results expand the knowledge of MR1 restricted γδ TCR’s shedding further light on the unusual docking modes that γδ TCR’s likely employ more broadly and provide key seminal insights into Vδ3 antigen recognition.

  1. (1) Le Nours, J. et al. A class of gammadelta T cell receptors recognize the underside of the antigen-presenting molecule MR1. Science 366, 1522-1527, doi:10.1126/science.aav3900 (2019).