A self MHC class II beta-chain peptide prevents diabetes in nonobese diabetic mice

Citation
P. Chaturvedi et al., A self MHC class II beta-chain peptide prevents diabetes in nonobese diabetic mice, J IMMUNOL, 164(12), 2000, pp. 6610-6620
Citations number
47
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
164
Issue
12
Year of publication
2000
Pages
6610 - 6620
Database
ISI
SICI code
0022-1767(20000615)164:12<6610:ASMCIB>2.0.ZU;2-O
Abstract
We explored T cell responses to the self class II MHC (I-A(g7)) beta-chain- derived peptides in diabetic and prediabetic nonobese diabetic (NOD) mice. We found that one of these immunodominant epitopes of the beta-chain of I-A (g7) molecule, peptide 54-76, could regulate autoimmunity leading to diabet es in NOD mice. T cells from prediabetic young NOD mice do not respond to t he peptide 54-76, but T cells from diabetic NOD mice proliferated in respon se to this peptide. T cells from older nondiabetic mice or mice protected f rom diabetes do not respond to this peptide, suggesting a role for peptide 54-76-specific T cells in pathogenesis of diabetes. We show that this pepti de is naturally processed and presented by the NOD APCs to self T cells, Ho wever, the peptide-specific T cells generated after immunization of young m ice regulate autoimmunity in NOD mice by blocking the diabetogenic cells in adoptive transfer experiments. The NOD mice immunized with this peptide ar e protected from both spontaneous and cyclo-phosphamide-induced insulin-dep endent diabetes mellitus, Immunization of young NOD mice with this peptide elicited T cell proliferation and production of Th2-type cytokines, In addi tion, immunization with this peptide induced peptide-specific Abs of IgG1 i sotype that recognized native I-A(g7) molecule on the cell surface and inhi bited the T cell proliferative responses. These results suggest that I-A be ta(g7)(54-76) peptide-reactive T cells are involved in the pathogenesis of diabetes, However, immunization with this peptide at young age induces regu latory cells and the peptide-specific Abs that can modulate autoimmunity in NOD mice and prevent spontaneous and induced diabetes.