טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentPatoka Renana
SubjectDevelopment of Methods for Evaluation of the Immunogenic
Potential of Cancer MHC Peptides by MHC
Microarrays
DepartmentDepartment of Biology
Supervisor Professor Arie Admon


Abstract

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.