Exploring The Contribution Of The Immunoproteasome To Immunodominance And T Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
The immunoproteasome is a piece of cellular machinery which degrades proteins and has been shown to enhance the body's recognition and response to viruses and cancer cells. This immunoproteasome is made up of various subunits, but it has not yet been assessed how each of these subunits contribute to the overall response. By studying the individual subunits, we will have a better understanding in how to manipulate the immune system for anti-viral and anti-cancer vaccine design.
Immunodominance In Vaccinia Virus And Recombinant Vaccinia Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$388,455.00
Summary
When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do ....When confronted with an invading microbe, the human immune system does not recognise its overall shape. Instead, the microbe is chopped up into tiny fragments, called peptides, and these can be recognised by special cells of the immune system called T cells which orchestrate a response. We have a good understanding of this chopping process and can predict many of these peptides, but this is only part of the story. Not all peptides will be recognized by a T cell. Further, through processes we do not understand well, T cells that recognize only a few out of the many peptides will dominate an entire immune response. As a result, immune responses are focused in such a way that they recognize only a tiny portion of an invading microbe. Focusing of immune responses also occurs during immunization with vaccines. Some new, genetically engineered vaccines use a harmless microbe to carry small parts of more dangerous pathogens. The parts chosen will not cause any disease by themselves, so the whole vaccine is safe. Vaccines built in this way are in clinical trials for diseases such as AIDS and malaria, but do not work as well as was hoped. These new vaccines are largely made up of the carrier and the parts of the microbe we wish to immunize against (e.g. a part of the AIDS virus) will be only a small fraction of the whole vaccine. Ideally we would like the immune system to focus on this small part of our choosing, but the few studies done suggest that this is not the case. In this project we will study vaccines that use a carrier called vaccinia virus. We will test to what extent immune responses are focused inappropriately. We will then genetically alter the virus and use new immunisation strategies to try and shift the focus of the immune response so that it targets the right parts of the vaccine. The ultimate aim is to improve vaccines, but in the process we may learn more about how the immune system chooses its targets.Read moreRead less
The Mechanisms Of Establishing, Maintaining Immunological Memory And Immunodominance Hierarchy
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amoun ....The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amount-length of antigen exposure; and the influence on memory induction from various immune modulators (cytokines) at the time of antigen encounter. Using a range of sophisticated detection methods, very early memory T cells will be identified in the primary response and tracked through their differentiation into long-term memory pool. Experiments will determine how T cells against particular determinants are selected from the primary immune response, retained in the memory pool and recalled in the subsequent challenges. The properties of antigen processing of various determinants will be correlated with the immunodominance hierarchy in the primary and memory response. Taken together the proposed project is central to understanding how memory T cells are created and what rules govern their stability. The project is highly relevant to vaccine design against tumours and pathogensRead moreRead less