Recognition of a microbial glycolipid antigen by both Type 1 and Type 2 NKT cells   — ASN Events
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Recognition of a microbial glycolipid antigen by both Type 1 and Type 2 NKT cells   (#99)

Catarina F Almeida 1 2 , Srinivasan Sundararaj 3 4 , Jerome Le Nours 3 4 , Onisha Patel 3 4 , Benjamin Cao 5 , Daniel Pellicci 1 2 , Spencer Williams 5 , Jamie Rossjohn 3 4 6 , Adam Uldrich 1 2 , Dale Godfrey 1 2
  1. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne , Melbourne, VIC, Australia
  2. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, VIC, Australia
  3. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences , Monash University, Melbourne, Clayton, Australia
  4. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Monash, VIC, Australia
  5. School of Chemistry , Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia
  6. Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK

Natural Killer T (NKT) cells are T cell lymphocytes that recognise lipid antigens presented by the MHC Class I-like molecule CD1d. There are two broad types of NKT cells: Type 1 NKT cells, which display limited T cell receptor (TCR) diversity and recognise a common lipid-Ag: α-Galactosylceramide α-GalCer), while Type 2 NKT cells express diverse TCRs and do not recognise α-GalCer. It is generally considered that there is no overlap between the lipid antigens that these two types of NKT cells recognize. However, here we demonstrate that the microbial-derived lipid-Ag α-glucuronosyl-diacylglycerol-(α-GlcA-DAG) can be recognized by subsets of both Type 1 and Type 2 NKT cells as well as a population of Vα10Jα50 T cells that fall between Type 1 and Type 2 NKT cells, as we have previously described. Single-cell TCR sequencing and the generation of TCR-transduced cell lines confirmed the diversity of TCRs that are capable of recognizing and responding to this antigen. Furthermore, through examination of the interaction with a panel of CD1d mutant molecules, combined with x-ray crystallographic analysis we revealed that Type 2 NKT cell TCRs can interact with CD1d plus α-GlcA-DAG in a similar manner to the highly conserved docking mode displayed by Type 1 NKT TCRs. Taken together, these data show that Type 2 NKT cells can detect a spectrum of lipid antigens presented by CD1d using a range of CD1d-docking modes.