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 t o glutamic acid decarboxylase (GAD) play an important role in insulin- dependent diabetes mellitus (IDDM) in NOD mice. However, specific epit opes responsible for eliciting these responses remain unresolved. In t his study, the T-cell epitopes involved in GAD-specific immune respons es in NOD mice were characterized. By priming NOD mice with GAD65, thr ee new GAD65 epitopes (GAD65 78-97, GAD65 202-221, GAD65 217-236) dist inct from those previously reported were found. Furthermore, our inves tigations into the fine determinant specificity of GAD67 revealed two additional GAD67-specific peptide epitopes (GAD67 25-47, GAD67 42-61). Two of the GAD65 epitopes (GAD65 202-221 and GAD65 217-236) are share d between GAD65 and GAD67. Spontaneous immune responses to these pepti des were found in pre-diabetic and diabetic mice and differential patt erns of responses to these peptides were observed depending on the age of the mice, disease status, or if the mice were protected from diabe tes by adjuvant immunotherapy. Characterization of these new epitopes will help in the elucidation of autoimmune responses to GAD in IDDM. ( C) 1998 Academic Press Limited.