A Conformationally-Constrained MHC Class II I-Ag7-Derived Peptide Protects NOD Mice from the Development of Diabetes

Allele-specific peptide vaccination against disease-associated MHC class II molecules is a promising new strategy for modulating self-antigen presentation to autoreactive T cells in autoimmune diseases. To evaluate the potential of this approach for treatment of insulin-dependent diabetes mellitus (...

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Veröffentlicht in:Journal of autoimmunity 1999-06, Vol.12 (4), p.233-242
Hauptverfasser: Dunsavage, Melina B, O’Leary, Cornelius J, Baumgart, Trageen D, Solvason, Nanette, Howard, Maureen, Lafferty, Kevin, Deshpande, Shrikant, Reich, Eva-Pia
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Sprache:eng
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Zusammenfassung:Allele-specific peptide vaccination against disease-associated MHC class II molecules is a promising new strategy for modulating self-antigen presentation to autoreactive T cells in autoimmune diseases. To evaluate the potential of this approach for treatment of insulin-dependent diabetes mellitus (IDDM), we have designed a cyclic peptide vaccine, DiavaX, from the third hypervariable region of the β-chain of the NOD mouse MHC class II I-Ag7. NOD mice were treated at 5 and 9 weeks of age with 100μg DiavaX emulsified in alum, a control peptide in alum, or alum alone. At the end of the study, 87% of alum treated mice had developed diabetes, compared with only 28% of DiavaX-treated mice. None of the control peptides, including a linear I-Ag7, a scrambled cyclic I-Ag7, or an analogous cyclic I-Aspeptide, reduced the incidence of diabetes, demonstrating that the protective effect of DiavaX is conformationally dependent and both allele- and sequence-specific. DiavaX treatment did not cause any general immune suppression, but did induce peptide-specific antibodies and memory T cells. DiavaX-induced protection from diabetes was associated with the maintenance of a non-destructive islet-associated autoimmune response. These data indicate that a conformationally constrained peptide from the disease-associated MHC represents a potential vaccine candidate for the prevention of clinical IDDM.
ISSN:0896-8411
1095-9157
DOI:10.1006/jaut.1999.0277