Professor James McCluskey, Dr Jamie Rossjohn
University of Melbourne
The immune system can sometimes identify cancerous cells and kill them
through "immune surveillance". In some cases, even established tumours
can be eradicated by immune cells that infiltrate the tumour and kill
off the malignant cells. However the immune system usually requires
signals such as inflammation that engenders activation of cells in
order to achieve this outcome.
A key goal in the field of tumour immunology is to understand the
mechanisms by which tumour cells are eliminated by the activated immune
system. In particular it is important to know the different cell types
responsible for tumour elimination, how these cells are activated and
how they discriminate tumour cells from normal tissues. In this
research project we will focus on one aspect of this process mediated a
novel set of T lymphocytes known as NKT cells.
These NKT cells are believed to be important in facilitating immunity
to a variety of tumours, through the recruitment of other cell types
and perhaps via direct tumour recognition. NKT cells essentially have a
single type of receptor for recognizing tumour molecules. This receptor
is the same in all individuals and recognizes a molecule called CD1d
that binds glycolipids and other small molecules manufactured by living
cells. It is unclear how this receptor binds the CD1d molecule and what
allows it to differentiate between normal glycolipids and those that
induce anti-tumour immunity.
It is also not known whether the tumours themselves make the
glycolipids that are recognized by NKT cells. We will determine the
3-dimensional structure of the human NKT receptor by itself and when it
is bound to a CD1d-glycolipid complex.
By engineering the NKT receptor we hope to be able to use this as a
reagent to scan for cells expressing the tumour glycolipid. A knowledge
of the structure of NKT cell receptors bound and unbound to their
target molecule (CD1d/glycolipid) will be of fundamental importance in
the field of tumour immunity.
Award / Duration
Research Grant: 2006-2008
$70,000 per annum