SIMILAR PEPTIDES FROM 2 BETA-CELL AUTOANTIGENS, PROINSULIN AND GLUTAMIC-ACID DECARBOXYLASE, STIMULATE T-CELLS OF INDIVIDUALS AT RISK FOR INSULIN-DEPENDENT DIABETES
- Author(s)
- Rudy, G; Stone, N; Harrison, LC; Colman, PG; McNair, P; Brusic, V; French, MB; Honeyman, MC; Tait, B; Lew, AM;
- Details
- Publication Year 1995-09-01,Volume 1,Issue #6,Page 625-633
- Journal Title
- MOLECULAR MEDICINE
- Publication Type
- Journal Article
- Abstract
- Background: Insulin (1) and glutamic acid decarboxylase (GAD) (2) are both autoantigens in insulin-dependent diabetes mellitus (IDDM), but no molecular mechanism has been proposed for their association. We have identified a 13 amino acid peptide of proinsulin (amino acids 24-36) that bears marked similarity to a peptide of GAD65 (amino acids 506-518) (G. Rudy, unpublished). In order to test the hypothesis that this region of similarity is implicated in the pathogenesis of IDDM, we assayed T cell reactivity to these two peptides in subjects at risk for IDDM. Materials and Methods: subjects at risk for IDDM were islet cell antibody (ICA)-positive, first degree relatives of people with insulin-dependent diabetes. Peripheral blood mononuclear cells from 10 pairs of at-risk and HLA-DR matched control subjects were tested in an in vitro proliferation assay. Results: Reactivity to both proinsulin and GAD peptides was significantly greater among at-risk subjects than controls (proinsulin; p < 0.008; GAD: p < 0.018). In contrast to reactivity to the GAD peptide, reactivity to the proinsulin peptide was almost entirely confined to the at-risk subjects. Conclusions: This is the first demonstration of T cell reactivity to a proinsulin-specific peptide. In addition, it is the first example of reactivity to a minimal peptide region shared between two human autoimmune disease-associated self antigens. Mimicry between these similar peptides may provide a molecular basis for the conjoint autoantigenicity of proinsulin and GAD in IDDM.
- Publisher
- BLACKWELL SCIENCE PUBL INC CAMBRIDGE
- Keywords
- PANCREAS BIOPSY SPECIMENS; ELEVATED PROINSULIN; AUTOIMMUNE-DISEASE; INTERFERON-GAMMA; IDDM PATIENTS; MELLITUS; AUTOANTIBODIES; ANTIBODIES; IDENTIFICATION; EXPRESSION
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Creation Date: 1995-09-01 12:00:00