A disease-associated cellular immune response in type 1 diabetics to an immunodominant epitope of insulin

• Published in: The Journal of clinical investigation Vol. 107; no. 2; pp. 173 - 180
• Main Authors: Alleva, D G, Crowe, P D, Jin, L, Kwok, W W, Ling, N, Gottschalk, M, Conlon, P J, Gottlieb, P A, Putnam, A L, Gaur, A
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-01-2001
• Subjects: Adolescent; Adult; Cells, Cultured; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - immunology; Female; Humans; Immunodominant Epitopes - pharmacology; Insulin - pharmacology; Interferon-gamma - immunology; Lymphocyte Activation - drug effects; Male; Peptide Fragments - pharmacology; Prediabetic State - blood; Prediabetic State - immunology; Risk Factors; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0021-9738
• DOI: 10.1172/jci8525

The 9-23 amino acid region of the insulin B chain (B9-23) is a dominant epitope recognized by pathogenic T lymphocytes in nonobese diabetic mice, the animal model for type 1 diabetes. We describe herein similar (B9-23)-specific T-cell responses in peripheral lymphocytes obtained from patients with recent-onset type 1 diabetes and from prediabetic subjects at high risk for disease. Short-term T-cell lines generated from patient peripheral lymphocytes showed significant proliferative responses to (B9-23), whereas lymphocytes isolated from HLA and/or age-matched nondiabetic normal controls were unresponsive. Antibody-mediated blockade demonstrated that the response was HLA class II restricted. Use of the highly sensitive cytokine-detection ELISPOT assay revealed that these (B9-23)-specific cells were present in freshly isolated lymphocytes from only the type 1 diabetics and prediabetics and produced the proinflammatory cytokine IFN-gamma. This study is, to our knowledge, the first demonstration of a cellular response to the (B9-23) insulin epitope in human type 1 diabetes and suggests that the mouse and human diseases have strikingly similar autoantigenic targets, a feature that should facilitate development of antigen-based therapeutics.