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.
Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.
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.
Using Influenza Vaccination To Understand And Improve Anti-viral Immunity In COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,316,597.00
Summary
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Lung infections often make those afflicted by COPD very unwell. We have recently shown that influenza vaccination induces a poor antibody response in many COPD patients. This study will examine why this is the case, and what can be done to restore normal immune function. In the final year of the Project, we will assess whether doubling the dose of influenza vaccination is helpful.
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.
An Investigation Into The Adaptive Immune Response In Celiac Disease
Funder
National Health and Medical Research Council
Funding Amount
$597,167.00
Summary
Celiac Disease (CD), an autoimmune-like disease that is triggered by the ingestion of dietary wheat gluten, or related proteins from rye and barely, affects ~1% of the population, causing tissue damage in the small intestine. The only available treatment is strict adherence to a lifelong gluten free diet. Our project aims to understand, at the molecular level, how components of the immune system and gluten interact to trigger the immune response that leads to CD symptoms.
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