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Epigenetic Regulation Of CD8+ T Cell Function And Memory.
Funder
National Health and Medical Research Council
Funding Amount
$578,171.00
Summary
Upon virus infection, a subset of white blood cells, called killer T cells, are recruited to fight the infection. This proposal aims to examine molecular changes that occur within killer T cells and impart their specific function. We also aim to understand how killer T cells are _programmed� as they establish immunological memory. This proposal will provide insights important for the design and improvement of vaccine strategies to fight pathogens such as influenza, HIV and even tumors.
Long-lived CD8 T Cell Responses Induced By A Recombinant Cytomegalovirus Vector
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this ....The priming of the immune system to protect against infection and disease is an important means to alleviate these conditions. Current vaccination technologies often rely on multiple inoculations (prime-boosting). In addition, specific priming of the immune system against pathogens that target mucosal sites has been difficult and often lacks efficacy resulting in temporary or variable protection. Using a well developed mouse model for a common human virus, we have explored the potential of this agent as a vaccine agent, making use of its long term persistence in the infected host to provide continued antigenic stimulation of the immune system. We have found that very strong and long lasting responses can be elicited after a single inoculation of avirulent virus. In this study, this effect will be further explored and developed.Read moreRead less
Investigations Into The Biology And Functionality Of The Human T Cell Receptor
Funder
National Health and Medical Research Council
Funding Amount
$424,262.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue and tumour cells through the use of specific cell surface receptors called T cell receptors (TCR). This project will study why partcular TCRs are used by the immune system, and will also examine the specificity of T cell recognition by determine the range of molecules an individual T cell can recognise. The work will aid in the development of new intelligent vaccines for cancer and infectious disease.
Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection ....Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection or tumour re-emerges. Little is known about the programming of memory CD8+ T cells. We have recently found that some of these cells have the potential to be reprogrammed to display different functions by exposure to new stimuli. This opens up the possibility that ineffective responses could be improved by using vaccination to control the production of these flexible or multipotential memory cells or to reprogram them once they are formed. Alternatively, effective responses might be subverted by pathogens to the detriment of the host. The goal of this project is to learn how the first exposure to an immune challenge influences the development of these multipotential memory CD8+ cells. Understanding the signals and processes that generate multipotential memory cells will be the first step towards developing ways to manipulate them to improve immune defence.Read moreRead less
The Genetics Governing The Specificity Of T Cell Receptors For Peptide-MHC
Funder
National Health and Medical Research Council
Funding Amount
$303,828.00
Summary
T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be ....T lymphocytes play a pivotal role in the immune system by recognising virus-infected tissue through the use of highly specific cell surface receptors. These T cell receptors (TCR) recognise viral peptides (p) presented by MHC molecules on the surface of virus-infected cells. For a TCR to be successfully triggered, it must lock onto an exact 3-dimentional pMHC match. In this way, any given TCR must simultaneously recognise both the viral peptide and the MHC presenting it. Such recognition must be sensitive and precise since a false positive could result in destruction of healthy tissue. There are a huge variety of TCRs and pMHCs, but there are only a few examples where the precise molecular interactions within the TCR-pMHC complex are known. Surprisingly, these studies have shown very limited consistency in the way the TCRs bind the pMHCs and therefore, the structural rules that underlie why TCRs consistently bind MHC remains a mystery of critical importance to this fundamental feature of the immune system. In this proposal, we will attempt to elucidate the rules of TCR-pMHC engagement. Another question to be addressed in this proposal is: During a viral infection, why are certain TCRs chosen above others that also have the capacity to recognise the same viral peptide? By investigating exactly which feature-s of these receptors predisposes their supremacy, we may be better able to predict the outcome of a pathogen attack and to even one day build our own super receptors. Finally, this proposal will also investigate how natural mutations in TCR genes across the human population affect our individual responses to viruses. Overall, advances in each of these core areas of medical research will aid in the development of new intelligent vaccines and individualised drugs for the treatment of cancer and infectious disease.Read moreRead less
Immune reactions are mediated by the expansion of white blood cells, and the progeny of this expansion is steered down different developmental pathways depending upon the nature of the initial infection or insult. We have recently identified a new means for control of the developmentwhite blood cells, and will here define this mechanism. These studies will open new opportunities for autoimmune therapeutics and vaccine development.