Characterization of Novel T-cell Epitopes on 65 kDa and 67 kDa Glutamic Acid Decarboxylase Relevant in Autoimmune Responses in NOD Mice

It has recently been shown that the T-cell mediated immune responses to glutamic acid decarboxylase (GAD) play an important role in insulin-dependent diabetes mellitus (IDDM) in NOD mice. However, specific epitopes responsible for eliciting these responses remain unresolved. In this study, the T-cell epitopes involved in GAD-specific immune responses in NOD mice were characterized. By priming NOD mice with GAD65, three new GAD65 epitopes (GAD65 78–97, GAD65 202–221, GAD65 217–236) distinct from those previously reported were found. Furthermore, our investigations into the fine determinant specificity of GAD67 revealed two additional GAD67-specific peptide epitopes (GAD67 28–47, GAD67 42–61). Two of the GAD65 epitopes (GAD65 202–221 and GAD65 217–236) are shared between GAD65 and GAD67. Spontaneous immune responses to these peptides were found in pre-diabetic and diabetic mice and differential patterns of responses to these peptides were observed depending on the age of the mice, disease status, or if the mice were protected from diabetes by adjuvant immunotherapy. Characterization of these new epitopes will help in the elucidation of autoimmune responses to GAD in IDDM.