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
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.
The introduction of novel viruses such as influenza and Henipa viruses into the human population from animal reservoirs is often fatal as the virus is not attenuated by adaptation to the host. As we are immunologically naïve, efficient immunity cannot be mounted. T cells mediate the control and clearance of viruses, and can remember past infection or vaccination. Understanding the role of T responses to zoonotic viral infections is needed for development of novel preventative vaccines.
Real Time Visualisation Of T Cell Cycling During Influenza Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$589,679.00
Summary
Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of an ....Influenza remains a major health threat, particularly in the elderly population. Here we will unravel the mechanisms underlying the expansion of killer T cells, a crucial part of the anti-influenza immune response. Using intravital multi-photon microscopy, we will follow the cell cycle dynamics of individual T cells in real time during different stages of influenza. We will further elucidate how ageing impacts on T cell proliferation. Together, this will provide insight into the mechanisms of anti-viral immunity and immuno-senescence.Read moreRead less
Mapping The Steps And Deciphering The Mechanisms Crucial In Dendritic Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$582,064.00
Summary
Dendritic cells (DCs) are a type of white blood that kick-start immune responses. There are various types of DCs that specialize in, for example, clearing viral, bacterial or fungal infections, and are even used to fight cancer. Understanding how DCs grow, therefore, has many clinical benefits. This project aims to understand these processes and identify new regulators of their growth using cutting edge technologies and strategies.
Immunoregulation And Adoptive Immunotherapy Of Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$391,784.00
Summary
This project is investigating link between a common herpesvirus and brain cancer. We are also aiming to develop new killer T cell-based therapy to target herpesvirus proteins in cancer cells with a long-term objective to use this information to develop a therpeutic vaccine against brain cancer.
Following The T Cell Repertoire Over The Human Life Course
Funder
National Health and Medical Research Council
Funding Amount
$473,159.00
Summary
T cells are critical to human health being our second and last line against infectious disease and cancer. However, we know very little about how this important immune compartment operates on a top-down scale. This project will use new technology to resolve this immune compartment to high detail. We will then use this new method to track the T cell compartment from the first years of life and across years of adult life to see how this vital immune compartment evolves along the human life course.
The Mechanisms Of SIV Entry Of Follicular Helper T Cells
Funder
National Health and Medical Research Council
Funding Amount
$95,313.00
Summary
Follicular helper T (Tfh) cells are a type of immune cells essential in antibody production. Preliminary data shows that SIV infects macaque Tfh cells. In this project, we will investigate the mechanisms by which SIV enters into Tfh cells, and test the susceptibility of human Tfh cells to HIV-1 infection ex vivo. This project will enable understanding of the fate of Tfh in HIV infection and its role in HIV host defense and it may facilitate the design of vaccine against HIV.
Determinants Of CTL Recruitment Into The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$474,647.00
Summary
The size of CD8+ T cell (CTL) responses is central to their efficacy in virus control, and can be substantially influenced by how effectively they are recruited and expand after infection. This study will determine the impact of both CTL characteristics and antigen abundance on CTL recruitment and expansion after infection. Understanding the nature of these influences will enable a more informed approach to the clinical manipulation of CTL responses.