Identification And Characterisation Of HLA-E Restricted Influenza A Virus-specific CD8+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$354,156.00
Summary
With seasonal epidemics and the continual threat of a pandemic, there is an urgent need for a one-shot universal vaccine that protects against different influenza strains. This can potentially be achieved by the activation of killer T cells. I will identify new virus targets presented by a highly conserved human protein. Killer T cell recognition of these targets may provide a unique opportunity to develop an improved vaccine.
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
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
Mechanisms That Control Epstein Barr Virus Infection And Their Dysregulation In X-linked Lymphoproliferative Disease
Funder
National Health and Medical Research Council
Funding Amount
$453,986.00
Summary
EBV is ubiquitous virus that infects more than 90% of the population worldwide. Although infection is largely asymptomatic in most healthy individuals, EBV is nonetheless associated with the development of at least 7 distinct types of human malignancies. Most importantly, EBV is still a huge healthy problem in conditions of immune suppression. Therefore a better understanding of the mechanisms involved in effective control of the virus will help develop better immune therapies and vaccines.
This fellowship is to support Professor Stephen Kent in generating new advances in vaccines to prevent HIV (the cause of AIDS) and Influenza (“The Flu”). HIV causes over 1.5 million deaths per year and no vaccine is currently available. Influenza causes around half a million deaths per year. Although the current Influenza vaccine is partially effective, improvements are needed for it to be able to protect against the many different strains of Influenza that can cause infection.
Using A Novel Assay That Detects Antigen Specific CD4+ And Regulatory T Cells To Further Understand Reconstitution Of Antigen Specific Immune Response Post Anti-retroviral Therapy In Subjects With HIV And In The Diagnosis Of Latent TB
Funder
National Health and Medical Research Council
Funding Amount
$102,780.00
Summary
The process by which the immune system recovers after commencement of therapy for HIV is not well understood. We will use a new test to monitor the immune system's ability to recognise and react to different antigens inorder to understand the factors that affect immune recovery in patients on therapy for HIV. We will also evaluate the use of this new test in the diagnosis of latent TB. Improvement in detection will lead to treatment of latent TB thus reduction of cases of active TB.