Altered B:9-23 insulin, when administered intranasally with cholera toxin adjuvant, suppresses the expression of insulin autoantibodies and prevents diabetes

M Kobayashi, N Abiru, T Arakawa, K Fukushima, H Zhou, E Kawasaki, H Yamasaki, E Liu, D Miao, FS Wong, GS Eisenbarth, K Eguchi

Research output: Contribution to journalArticle (Academic Journal)

29 Citations (Scopus)

Abstract

Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes that contains two distinct CD4 epitopes (B:9-16 and B:13-23). One of the two epitopes, B:13-23, overlaps with a CTL epitope (B:15-23). In this study, we report that the elimination of the CTL epitope from the B:9-23 peptide by amino acid substitution (with alanine) at positions B:16 and 19 (A16,19 altered peptide ligand) or truncation of the C-terminal amino acids from the peptide (B:9-21), neither of which stimulated the proliferation of insulin B:15-23 reactive CD8 T cells, provided significant intranasally induced suppression of diabetes when coadministered with a potent mucosal adjuvant cholera toxin (CT). Intranasal treatment with A16,19 resulted in the elimination of spontaneous insulin autoantibodies, significant inhibition of insulitis and remission from hyperglycemia, and prevented the progression to diabetes. Intranasal administration of native B:9-23/CT or B:11-23/CT resulted in a significant enhancement of insulin autoantibody expression and severity of insulitis and failed to prevent diabetes. Our present study indicates that elimination of the CTL epitope from the B:9-23 peptide was critically important for mucosally induced diabetes prevention. The A16,19 altered peptide ligand, but not other native insulin peptides, suppresses insulin autoantibodies associated with protection from and remission of diabetes.
Translated title of the contributionAltered B:9-23 insulin, when administered intranasally with cholera toxin adjuvant, suppresses the expression of insulin autoantibodies and prevents diabetes
Original languageEnglish
Pages (from-to)2082 - 2088
Number of pages7
JournalJournal of Immunology
Volume179 (4)
Publication statusPublished - Aug 2007

Bibliographical note

Publisher: American Association of Immunologists

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    Kobayashi, M., Abiru, N., Arakawa, T., Fukushima, K., Zhou, H., Kawasaki, E., Yamasaki, H., Liu, E., Miao, D., Wong, FS., Eisenbarth, GS., & Eguchi, K. (2007). Altered B:9-23 insulin, when administered intranasally with cholera toxin adjuvant, suppresses the expression of insulin autoantibodies and prevents diabetes. Journal of Immunology, 179 (4), 2082 - 2088. http://www.jimmunol.org/cgi/content/abstract/179/4/2082