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JDRF Funded Research

JDRF-Funded Research:  Lay Abstract

Name:   Peter Antinozzi ,Ph.D. , B.SC
Columbia University, USA
Lab Website:  

Project duration:   01-FEB-2003   to   30-JUN-2005
Postdoctoral Fellowship Award

Project grant award:   $96,781.00*

* Total Grant award amount may vary depending on budget adjustments and it is contingent upon research progress and availability of JDRF research funds.
File No:   3-2003-207

(Abstract Dt: 15-AUG-2002)

Therapeutic Area:   Immune Therapies

Grant Status: Inactive
Project Title
Understanding the development of autoimmune islet antibodies by evaluation of specific routes of intracellular beta-cell peptide recognition by the immune system.
Objective
To determine how the immune system specifically identifies the pancreatic beta-cell.
Background/Rationale
Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease in which the immune system mistakenly identifies and systematically eliminates the only cells in the body that produce insulin, the pancreatic beta-cells. Upon elimination of these cells, insulin must be administered through needles and/or pumps to maintain blood sugar levels for the lifetime of the patient. The specificity and completeness of the removal of the pancreatic beta-cells is remarkable in which neighboring non-beta-cells are left intact. This project is designed to understand how the immune system specifically recognizes the beta-cell.
Description of Project
Before insulin treatment is required, there are several early warning signs that a person is en route towards IDDM. One of these signs is the appearance of certain specific antibodies that accompany the immune response against the beta-cell. These antibodies are generally directed against components (antigens) that are inside the beta-cell. Being inside the cell, these antigens should not be accessible to the immune system, so it is therefore unusual that the immune system would mount an attack directed at them. Furthermore, numerous other cells in the body simultaneously contain these same exact antigens, however these cells are untouched by the immune system. One factor that may lead to development of these antibodies and eventual IDDM is that the beta-cell itself may present these identifying antigens to the attention of the immune system. Two distinct routes of self-presentation will be evaluated in this proposal: 1) translocation of an antigen that is normally on the inside of the cell to the outside and 2) a direct presentation of the antigen to the immune system. Recent studies have demonstrated that one particular component of cells, called Hsc70, may in fact assist in both of these proposed routes and will therefore be a focus of this study. A final goal of this proposal is to address these same possibilities by a high-throughput approach.
Anticipated Outcome
Thus, the goals of this proposal will explore two possible mechanisms in which the beta-cell hails the immune system. Based upon the insights obtained, strategies to reduce the capacity of the beta-cell to present antigens would be expected to impair the progression of the disease.