A Novel Role For MHC Class II In Carbohydrate Presentation
Funder
National Health and Medical Research Council
Funding Amount
$703,030.00
Summary
Cells of the immune system swallow up foreign molecules and break them down to smaller fragments. T cells then identify the degraded antigen fragments and coordinate the immune response. In this project we will investigate how the T cells identify carbohydrates.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
Quantification Of Antigen Presentation To CD8 T Cells During Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Knowledge of how virus-infected cells are detected by the bodyÍs immune system is fundamental to our understanding of virus infections and attempts to improve vaccines. We know that many proteins are displayed during virus infection but until now, the precise details of this display have only been worked out for very few proteins, studied one at a time. In this project we will apply cutting-edge technology to gain the first holistic view of how a virus-infected cell looks to the immune system.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
A Molecular Investigation Into Lipid-reactive Immunity To Combat Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,152.00
Summary
Tuberculosis (TB) infection currently causes ~1.5 million deaths annually. Due to new survival features acquired by the causative agent (Mycobacterium tuberculosis), traditional TB drugs and vaccines are becoming inefficient. Mycobacterium tuberculosis has a protective lipid-dense cell wall that is targeted by our immune system. We aim to understand the mechanisms of the lipid-mediated immune response to TB in order to develop more effective strategies to combat this disease.
Understanding The Development Of Autoimmunity In Response To Citrullinated Peptide Antigen Presentation To T Cells In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$1,181,793.00
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease predominantly affecting synovial joints, in 1% of adults worldwide. HLA-class II genes underlie the major genetic susceptibility to RA. The programme of work brings together 7 investigators from 3 countries to determine how autoimmunity develops to self antigens in individuals at genetic risk of RA and why resistance alleles are protective against RA, in Caucasian, Asian and North American Native populations. We will provide a molecular
Antigen Presentation During HLA B27 Associated Auotimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$715,365.00
Summary
Ankylosing spondylitis is a debilitating arthritic disease, susceptibility to which is conferred by genes of the immune system, particularly HLA-B27, and following gastrointestinal infection. Using mass spectrometry we will identify bacterial peptides bound to HLA-B27 on infected cells that may trigger an autoimmune response. Defining the self peptides that remain the targets of autoimmunity will unravel the molecular and cellular mechanisms if disease and identify peptides for immunotherapy.
Priming, Recruitment And Retention Of Influenza Virus Specific CD8 T Cells In The Upper Airways
Funder
National Health and Medical Research Council
Funding Amount
$633,371.00
Summary
Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the upper airways. This early stage of infection, when the amount of influenza virus is low, provides the ideal window of opportunity for an effective immune response to limit disease progression. In this proposal we will define the immunity that can be evoked within the upper airways and determine immune mechanisms left behind that can safeguard this region from this important respiratory pathogen
The Molecular Basis Of HLA-linked Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$827,536.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project continues to probe the mechanisms of immune mediated drug reactions by examining the basis of life threatening reactions to drugs used to treat epilepsy, gout and commonly used drugs such as penicillin and aspirin.
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.