CD8+ cytotoxic T-cells are thought to be critically involved in islet destruction in type I diabetes. This work is designed to identify peptide epitopes that are recognized by islet specific CD8+ T-cells. Cloned islet specific CD8+ T-cells from the islet lymphocytic infiltrate that recognizes both islets and immortalized NIT beta cell line have been and will continue to be generated and assessed for their ability to replace CD8+ polyclonal T-cells in disease transfer experiments. MHC Class I bound peptides will be isolated from NIT-cells as will a subset that is recognized by CD8+ T-cell clones.
In Specific Aim 2 the peptides will be tested for their ability to stimulate disease producing CD8+ T-cells. Synthetic peptides derived from the sequence of known beta cell autoantigens will also be tested.
In Aim 3 how cytokines and glucose induced beta cell secretory activity influence presentation of peptides and susceptibility to killing by CD8+ T-cells will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29DK049717-03
Application #
2713404
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Akolkar, Beena
Project Start
1996-06-01
Project End
2001-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Pharmacy
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089