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.