Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide

doi:10.1084/jem.177.5.1499

This Article

	Full Text (PDF, 532K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hurtenbach, U.
	Articles by Nagy, Z. A.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hurtenbach, U.
	Articles by Nagy, Z. A.


Social Bookmarking

	What's this?

ARTICLES

Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide

U Hurtenbach, E Lier, L Adorini and ZA Nagy
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.

The role of antigen presentation as a possible mechanism underlying major histocompatibility complex (MHC) association of autoimmune disease has been studied in non-obese diabetic (NOD) mice. By screening for inhibition of antigen presentation to NOD T cell hybridoma, we have selected a synthetic peptide, yTYTVHAAHAYTYt (small letters denote D amino acids), that efficiently blocks antigen presentation by the NOD class II MHC molecule A alpha g7A beta g7 (Ag7) in vitro. The inhibition is MHC selective, in that it does not affect antigen presentation by the E(d) and E(k) molecules, and has only a marginal effect on presentation by the A(d) molecule. This peptide also inhibits the priming for Ag7-restricted T cell responses in vivo, and prevents the spontaneous development of diabetes in female NOD mice, when administered chronically from 3 wk of age on. Chronic treatment with a control peptide, KMKMVHAAHAKMKM, that fails to bind to Ag7 has no effect on the disease. These data indicate that antigen presentation by the Ag7 molecule plays a pivotal role in the induction of autoimmune diabetes. Furthermore, the results demonstrate that interference with antigen presentation by a class II molecule can prevent the onset of spontaneous autoimmune disease associated with the same molecule.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

de Graaf, K. L., Barth, S., Herrmann, M. M., Storch, M. K., Otto, C., Olsson, T., Melms, A., Jung, G., Wiesmuller, K.-H., Weissert, R. (2004). MHC Class II Isotype- and Allele-Specific Attenuation of Experimental Autoimmune Encephalomyelitis. J. Immunol. 173: 2792-2802 [Abstract] [Full Text]
Overbergh, L., Decallonne, B., Branisteanu, D. D., Valckx, D., Kasran, A., Bouillon, R., Mathieu, C. (2003). Acute Shock Induced by Antigen Vaccination in NOD Mice. Diabetes 52: 335-341 [Abstract] [Full Text]
Trembleau, S., Gregori, S., Penna, G., Gorny, I., Adorini, L. (2001). IL-12 Administration Reveals Diabetogenic T Cells in Genetically Resistant I-E{alpha}-Transgenic Nonobese Diabetic Mice: Resistance to Autoimmune Diabetes Is Associated with Binding of E{alpha}-Derived Peptides to the I-Ag7 Molecule. J. Immunol. 167: 4104-4114 [Abstract] [Full Text]
Corper, A. L., Stratmann, T., Apostolopoulos, V., Scott, C. A., Garcia, K. C., Kang, A. S., Wilson, I. A., Teyton, L. (2000). A Structural Framework for Deciphering the Link Between I-Ag7 and Autoimmune Diabetes. Science 288: 505-511 [Abstract] [Full Text]
MURPHY, B., KRENSKY, A. M. (1999). HLA-Derived Peptides as Novel Immunomodulatory Therapeutics. J. Am. Soc. Nephrol. 10: 1346-1355 [Abstract] [Full Text]
Woulfe, S. L., Bono, C. P., Zacheis, M. L., Welply, J. K., Kirschmann, D. A., Baudino, T. A., Wang, Y., Stone, D. A., Hanson, G. J., Vuletich, J. L., Bedell, L. J., Schwartz, B. D., Howard, S. C. (1997). A Peptidomimetic that Specifically Inhibits Human Leukocyte Antigen DRB1*0401-restricted T Cell Proliferation. J. Pharmacol. Exp. Ther. 281: 663-669 [Abstract] [Full Text]
Harrison, L. C., Honeyman, M. C., Trembleau, S., Gregori, S., Gallazzi, F., Augstein, P., Brusic, V., Hammer, J., Adorini, L. (1997). A Peptide-binding Motif for I-Ag7, the Class II Major Histocompatibility Complex (MHC) Molecule of NOD and Biozzi AB/H Mice. JEM 185: 1013-1022 [Abstract] [Full Text]