2000年6月
Importance of GAD65 peptides and I-A(g7) in the development of insulitis in nonobese diabetic mice
IMMUNOGENETICS
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- 巻
- 51
- 号
- 7
- 開始ページ
- 538
- 終了ページ
- 545
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1007/s002510000173
- 出版者・発行元
- SPRINGER VERLAG
Insulin-dependent diabetes mellitus (IDDM) develops in nonobese diabetic (NOD) mice through the destruction of the B cells in pancreatic Langerhans islets by islet autoantigen-specific T cells. The islet autoantigen glutamic acid decarboxylase 65 (GAD65) is thought to be a major target autoantigen in IDDM. In the present report, we established GAD65-specific T-cell clones using overlapping peptides that cover the amino acid sequences of mouse GAD65. T-cell epitopes of GAD65 were characterized by proliferation and binding assays using various analogue peptides and wild-type or mutant I-A(g7) transfectants. The efficacy of the peptide vaccine in IDDM was determined by administering T-cell epitope peptides to NOD mice and evaluating the histopathology of their insulitis. We obtained two types of T-cell clone, one specific for peptide p316-335 and another specific for p531-545 of GAD65. The p531-545 site has already been identified, but we report the p316-335 site for the first time. T-cell clones recognized those peptides in the wild-type I-A(g7) but not in the mutant I-A(g7) in which the serine at position 57 of the beta-chain was replaced by an aspartic acid. Both the p316-335 and p531-545 peptides bound weakly to I-A(g7). Some peptides with amino acid substitutions had antagonistic activity, and administration of a large amount of wild-type peptide reduced the severity of insulitis in NOD mice. Our results suggest that peptide vaccine therapy may be useful in autoimmune diseases, including IDDM.
- リンク情報
- ID情報
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- DOI : 10.1007/s002510000173
- ISSN : 0093-7711
- Web of Science ID : WOS:000087930600004