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David G. Alleva, Paul D. Crowe, Liping Jin, William W. Kwok, Nicholas Ling, Michael Gottschalk, Paul J. Conlon, Peter A. Gottlieb, Amy L. Putnam, Amitabh Gaur
J Clin Invest. 2001;
107(2):173
doi:10.1172/JCI8525
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he 9–23 amino acid region of the insulin B chain (B(9-23)) is a dominant epitope recognized by pathogenic T lymphocytes in nonobese diabetic mice, the animal model for type 1 diabetes. We describe herein similar B(9-23)-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 B(9-23), 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 B(9-23)-specific cells were present in freshly isolated lymphocytes from only the type 1 diabetics and prediabetics and produced the proinflammatory cytokine IFN-γ. This study is, to our knowledge, the first demonstration of a cellular response to the B(9-23) 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.
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