A STRUCTURAL INVESTIGATIONS INTO EVENTS WITHIN THE IMMUNOLOGICAL
SYNAPSE
Jamie Rossjohn
The Protein Crystallography Unit, Monash Centre for Synchrotron Science, Department
of Biochemistry & Molecular Biology, School of Biomedical Sciences, Monash
University, Clayton, Victoria 3800, Australia
Typically, a cell’s viability is governed by interactions between cell surface receptors
and their cognate ligands, which generally leads to activation of intracellular signal
transduction cascades and ultimately enhanced transcription of genes involved in
cellular proliferation. Globally, how such receptor-mediated recognition events translate
to intracellular signalling is a poorly understood phenomenon in any biological system,
and is especially complex in the context of cellular immunity.
T lymphocytes (T-cells), an essential cellular component of the immune system,
play a fundamental role in the elimination of invading micro-organisms. The cytotoxic
T-cell (CTL) response towards viruses is directed towards class I Major
Histocompatibility Complex (MHC-I) molecules complexed to viral peptide antigens
(p-MHC-I). These complexes are expressed on the surface of infected cells and are
subsequently recognised specifically by clonally distributed  T cell receptors (TcR)
on CD8+ T-cells. Appropriately armed and activated CD8+ T-cells can eliminate
infected cells and prevent viral replication. The formation of the specific TcR/p-MHC-I
complex is the central event of antigen recognition in the cellular immune response that
activates the antigen-specific CTL.
However, this central TcR/p-MHC-I recognition event alone is not sufficient to initiate
intracellular signalling, but requires the recruitment of a host of co-receptors and
accessory molecules. The formation of this co-ordinated, receptor-mediated corecognition event, termed the immunological synapse, is exquisitely complex, however
the structural basis for the formation of the immunological synapse is poorly defined.
A major focus of research within the laboratory is to gain a full atomic understanding of
the events central to the formation of the immunological synapse. This presentation
will highlight some of our recent salient findings.