The immune system is the essential complex barrier that protects the organism for infections and some malignancies. Despite considerable efforts, the mechanism by which immune cells kill dangerous unwanted cells is poorly understood. This project will investigate the mechanism of action and the role in human pathologies of a key component of the immune system, a toxic protein perforin.
Vaccines that deposit memory T cells within the lung, gut and genital tract hold enormous therapeutic potential, as these mucosal surfaces are major portals of entry into the body for many viruses. However, the accumulation of large numbers of T cells within the mucosal tissue may increase the number of target cells for T cell trophic viruses (eg HIV) to infect. We will explore factors that result in the generation of mucosal memory T cells that are resistant to virus infection.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
We know that many parts of viruses are displayed to the immune system, but infection can also result in the display of fragments of our body's own proteins (self-peptides). We will apply cutting-edge technology to find all the virus- and self-peptides that are recognised by the immune system during infection with a vaccine virus and influenza virus. This will help us understand how the body fights infection and perhaps why infection can sometimes start autoimmune diseases.
A Novel CCR2-dependent Niche For CD8+ T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$482,549.00
Summary
In this project, we will determine how a protein called CCR2 controls the generation of memory immune responses and whether its activity can be manipulated to enhance vaccination.
Perforinopathy: Immune-disease Due To Defective Perforin Function
Funder
National Health and Medical Research Council
Funding Amount
$671,514.00
Summary
White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should addre ....White blood cells called cytotoxic lymphocytes destroy cancerous cells using special toxic molecules. One of them, perforin, eliminates dangerous cells by punching holes in their membrane. Some individuals that lack perforin become seriously ill in their infancy. Others, that retain some perforin in their lymphocytes can live longer and are at higher risk of developing cancer. We will investigate the causes of partial loss of perforin function and explore novel drug therapies, which should address the problem and restore immune function.Read moreRead less
The Role Of Long Peptide Epitopes In Antiviral CD8+ T Cell Recognition.
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
The immune response to viral infection involves killer T cell recognition of small viral peptides presented by infected cells. Researchers have been attempting to identify the viral peptides that are recognised by T cells. Although these studies have been successful, the major aim of this project is to investigate if the role of unusually long peptides has been underestimated. This project should lead to enhanced monitoring of immune responses and improvements in vaccine design.
Follicular Cytotoxic T Cell Differentiation And Function In Infection And B-cell Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$963,892.00
Summary
Cytotoxic T cells eliminate infected or cancerous cells, constituting a major arm of the immune defence. In this study, we will investigate a subset of cytotoxic T cells that particularly migrate into B cell follicles to control infection and malignancy. Understanding of the differentiation and function of this subset, termed as follicular cytotoxic T (TFC) cells, will help us to develop new strategies to treat EBV and HIV infections as well as B cell lymphomas.
A New Approach To The Design And Evaluation Of T Cell Vaccines For Cancer And Infectious Disease.
Funder
National Health and Medical Research Council
Funding Amount
$394,137.00
Summary
Special white blood cells called dendritic cells teach the immune system to fight cancer and are a key component of therapeutic cancer vaccines. We identified a subtype of human dendritic cell that is predicted to be the most effective at mounting anti-cancer immune responses. We developed a novel antibody specific for these dendritic cells that can be used to deliver the vaccine directly to them and will use this to construct and validate a novel vaccine for cancer and viral infections.
Determining The Biological Significance Of Allelic Sequence Variation Within The T Cell Receptor Loci
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific T cell receptors (TCRs). This project will investigate the importance of genetic variation in the TCR genes in influencing how we fight infections. Advances in these areas will assist in understanding susceptibility to some autoimmune diseases as well as aiding in the development of new "intelligent" vaccines and individualised therapeutics.