T-cells are a key component of our immune system. Natural killer T-cells, also known as NKT cells, are implicated in a broad range of diseases and health conditions, including microbial immunity, tumour immunity, autoimmunity and allergy. While T-cells recognise peptide-based antigens such as foreign proteins, NKT cells recognise lipid-based (fat-based) antigens.
The discovery of this new NKT cell type within our immune system has important implications for our understanding of how NKT cells actually work and how we might use this improved understanding to combat immune diseases.
Melbourne University, Monash University and Peter MacCallum Cancer Centre researchers used x-ray crystallography at the Australian Synchrotron to determine key structural details of how the T-cell receptor found on the surface of NKT cells interacts with the lipid antigen that is presented by a molecule called CD1d.
Left: The newly discovered Vα10 natural killer T-cell bound to a glycolipid antigen (crystal structure of V(alpha)10-V(beta)8.1 NKT TCR in complex with Cd1d- alphaglucosylceramide). Image courtesy of Jamie Rossjohn.
PBD code: 3RUG (http://www.rcsb.org/pdb/explore/explore.do?structureId=3RUG)
NKT cells are traditionally divided into two groups according to the type of T cell receptor (TCR) found on the cell surface. It is the TCR structure that determines which kind of glycolipid antigens (foreign molecules such as the sugars that make up bacterial cell walls) they can recognise.
The new NKT cell type – Vα10 – identified by a research team headed by Dale Godfrey (Melbourne University), Jamie Rossjohn (Monash University) and Mark Smyth (Peter MacCallum Cancer Centre) is similar in some respects to previously characterised NKT cells, but differs in the way it recognises diverse glycolipid antigens.
The team worked with collaborators in the UK and US to determine the atomic structure of Vα10 in complex with a glycolipid antigen to gain insight on how this new cell type binds to glycolipid antigens.
The work was published in a highly-regarded international publication called Nature Immunology in June 2011. Click here to view.