|M.Sc Student||Patoka Renana|
|Subject||Development of Methods for Evaluation of the Immunogenic|
Potential of Cancer MHC Peptides by MHC
|Department||Department of Biology||Supervisor||Professor Emeritus Arie Admon|
The Major Histocompatibility Complex (MHC) is a glycoprotein shuttle that present peptides derived from the cell’s proteins for scrutiny by T-lymphocyte. Cancer cells present both normal and abnormal peptides, derived from genetic changes in the cancer cells. The abnormal peptides can induce a Cytotoxic T lymphocyte (CTL) reaction useful for immunotherapy, based on vaccination with tumor antigens.
Significant effort is being made to identify those peptides that can be used in cancer treatment. As a result of these efforts a vast amount of information has accumulate. A major problem is evaluating the immunogenic potential of identified peptides. Such evaluation depends on use of T cells from cancer patients and the number of such T cells that can be obtained from the patients is limited.
In this research we began to develop novel high-throughput scanning methods for immunogenic peptides, base on microarray technology. The microarray is composed of MHC-peptide complexes and cytokine-capture antibodies, arrayed on a PVDF membrane. MHC-peptide complexes activate the corresponding T-cells, which in response secret cytokines to the growth media. Cytokine-capturing antibodies than capture the cytokines at their secretion site. This way, MHC peptides that can activate the T-cells can be identified. In addition, we began developing a method that will allow an easy construction of MHC-peptide complexes. The method is based on construction of primary complex, from which the original peptide can be easily extracted and exchanged with a new one. Furthermore, the peptide exchange method will allow us to collect the MHC peptides directly from the mass spectrometer, used to identify the peptides.