|M.Sc Student||Scheinmann Tali|
|Subject||Isolation and Characterization of a TCR-like|
Antibody Targeting a Self-Peptide
|Department||Department of Biology||Supervisor||Professor Yoram Reiter|
|Full Thesis text|
The presentation of self-peptide on MHC complexes in the periphery to potentially auto reactive T cells that have escaped negative selection in the thymus constitutes a major problem to the immune system. In order to control their reactivity and preserve immune tolerance, mechanisms of elimination and functional inactivation operate in the periphery.
Previous work in our lab revealed that high presentation of differentiation antigens in melanoma cells (such as MART1 and gp100) induces hyporesponsiveness in CTLs. It was found that the function of killing initiates at very low antigen density and reaches optimum at around 100 MHC-peptide complexes. However, when ~250 MHC-peptide complexes were presented by the target cell, a significant inhibition of CTL activity was observed that was characterized by long-term decrease in cytotoxic activity, inhibition of proliferation and anergy.
The influence of high antigen densities on normal tissues was never examined in the context of CTL's cytotoxicity and peripheral tolerance. Our aim in this study is to quantify the presentation of central self-derived peptides in normal tissues, characterize the presentation of key peptides on different tissues and study the role of high self-peptides densities in peripheral tolerance. By using specific TCR-like antibodies against self-peptides chosen on the basis of MS analysis, we will quantify and characterize the presentation of antigens. CTLs against the highly presented peptides will be exposed to increasing antigen densities and their lytic activity and responsiveness will be examined to determine their killing optimum and pattern. This study may shed new light on the influence of antigen densities in the context of peripheral tolerance.