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The Insulin-Specific T Cells of Nonobese Diabetic Mice Recognize a Weak MHC-Binding Segment in More Than One Form¹

Matteo G. Levisetti^*,, Anish Suri, Shirley J. Petzold and Emil R. Unanue^2,

^* Department of Medicine and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Several naturally occurring anti-insulin CD4 T cells were isolated from islet infiltrates of NOD mice. In accordance with the results of others, these T cells recognized the segment of the -chain from residues 9–23. Peptides encompassing the B:(9–23) sequence bound weakly to I-A^g7 in two main contiguous registers in which two residues at the carboxyl end, P20Gly and P21Glu, influenced binding and T cell reactivity. Naturally occurring insulin-reactive T cells exhibited differing reactivities with the carboxyl-terminal amino acids, although various single residue changes in either the flanks or the core segments affected T cell responses. The insulin peptides represent another example of a weak MHC-binding ligand that is highly immunogenic, giving rise to distinct populations of autoimmune T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health grants and by the Kilo Diabetes and Vascular Research Foundation.

² Address correspondence and reprint requests to Dr. Emil R. Unanue, Campus Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail address: unanue{at}pathbox.wustl.edu

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