Tapasin And Major Histocompatibility Complex Class I Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. ....An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. This research proposal aims to examine the role of tapasin in this regard. A thorough understanding of the basic principles of peptide presentation to T cells is crucial to the design of effective vaccines. Furthermore it will also broaden our understanding of immunological responses to cancer, autoimmune diseases and infections.Read moreRead less
The Unique Nature Of Gamma Delta T Cell Recognition Resolved Through Interaction With H2-Q10
Funder
National Health and Medical Research Council
Funding Amount
$699,031.00
Summary
The liver is important for both digestion and immunity. Given these opposing functions, the liver must exert control points that prevent the immune system from recognising food products. We have now identified a new molecular target that controls the development of immune cells in the liver.
Unraveling The Link Between HLA B27 And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$746,102.00
Summary
Ankylosing spondylitis and related diseases cause significant morbidity in up to 0.25% of the population. Current treatments have limited efficacy and often debilitating side effects. More targeted peptide antigen based therapies will have fewer side effects and would be of major clinical importance to this group of diseases. This project seeks to identify peptide antigens that could be used in targeted immunotherapy. We also seek to understand how some of the idiosyncratic properties of HLA B27
Crystallographic Studies Of Non-canonical Peptides Binding To MHC Class I Molecules.
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
Virus infected cells and cancer cells are recognised and eliminated from our body by specialised cells called T-cell lymphocytes. This recognition process is the key step in the immune response and some fundamental questions in immunology are centred on the nature of this process. At the molecular level, the recognition is mediated by the specific interaction between proteins on the surface of the cells. On the T-cell lymphocyte, the T-cell receptor (TCR) binds specifically to a protein called t ....Virus infected cells and cancer cells are recognised and eliminated from our body by specialised cells called T-cell lymphocytes. This recognition process is the key step in the immune response and some fundamental questions in immunology are centred on the nature of this process. At the molecular level, the recognition is mediated by the specific interaction between proteins on the surface of the cells. On the T-cell lymphocyte, the T-cell receptor (TCR) binds specifically to a protein called the MHC on the surface of the target cell. The target cell can be a cancer cell, or an infected antigen presenting cell (specialised cells in the body which present protein fragments (peptides) on their surface via MHC). The structure of a TCR and TCR-MHC have been solved in terms of the shape of the molecules at atomic resolution, bringing detailed information on how these two proteins interact with each other. In this proposal the structural basis of antigen presentation and recognition in cell-mediated immunity will be determined by three-dimensional structures of different peptides on MHC by x-ray crystallography. Cell surface antigen presentation by MHC molecules is crucial for initiating the cellular immune response against invading pathogens and cancer. This proposal encompasses a combined biochemical, immunological, and biophysical approach to understand the range of ligands which can bind to MHC which are subsequently recognised by the TCR. To understand the antigenic properties of modified peptides at the structure level, the x-ray structure of MHC with modified bound synthetic peptides will be determined.Read moreRead less
The liver is an important organ in terms of immune responses. Owing to its exposure to many antigens, it is required to maintain a form of immune tolerance. This ensures that overt immune responses which would damage the liver do not occur. One means by which tolerance occurs is through silencing killer cells through the regulation of molecules of Major Histocompatibility Complex (MHC). This project will explore the role of a soluble form of MHC which is expressed only in the liver.
Structural Investigation Of The Major Histocompatibility Complex Class I Peptide-loading Complex
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
The identification and destruction of diseased cells by our immune system is essential to controlling the spread of infection. This proposal is aimed at the characterisation of the peptide-loading complex (PLC), a large molecular machine that facilitates a crucial step in the process of ‘flagging’ infected cells. Determining the 3D structures of its key components, as well the way in which they interact will help us understand how the PLC contributes to maintaining our body’s health.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$14,927,045.00
Summary
This program focuses on understanding the development of immunity during infection or inflammatory diseases using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune or inflammatory diseases.
Structural And Functional Characterisation Of The Killer Cell Immunoglobulin-like Receptor (KIR) Family Of Natural Killer Cell Receptors
Funder
National Health and Medical Research Council
Funding Amount
$348,070.00
Summary
Natural Killer (NK) cells are an important component of the immune response to cancer and infection. This project will define the molecular targets that are recognised by NK cells. This knowledge can then be used to guide in the selection of bone marrow donors in the treatment of leukemias as well as understanding how we fight off infections.