Title

Interaction of heat shock proteins with antigen presenting cells

Date of Completion

January 2000

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

The study on the mechanism (Udono et al, 1994) that leads to tumor resistance upon immunization of mice with tumor derived gp96 preparations showed that antigen presenting cells (APCs) are important in the immunogenicity of gp96. As exogenously administered soluble gp96-peptide complexes were found to enter the MHC I pathway of antigen presentation (Suto et al, 1995), the intracellular events involved in this pathway are of keen interest. Studies were undertaken to test the effect of proteasome inhibitors and the role of TAP complex in the context of re-presentation of peptides chaperoned by heat shock protein gp96. In light of the observation that immunogenicity of gp96 preparations from tumor cells is due to the peptides bound to gp96, studies were undertaken to test whether CRT, another peptide binding protein of the endoplasmic reticulum by virtue of its peptide-binding ability and being a HSP can elicit tumor immunity when purified from tumor cells. Lastly, in this study it is shown for the first time that the interaction of mammalian HSPs with APC in vitro leads to stimulation of the APCs in a non-specific manner. This non-specific interaction excludes the role of peptides chaperoned by the HSPs. ^