Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401
Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401
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DOI：
10.1172/jci119079
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发表时间：
1996-12-01
影响因子：
15.9
通讯作者：
Whiteley, PJ
中科院分区：
文献类型：
--
作者：
Wicker, LS;Chen, SL;Whiteley, PJ
从自身免疫性疾病相关抗原中鉴定II类结合肽表位是开发抗原特异性免疫调节治疗的重要步骤。在I型糖尿病的情况下，T细胞和B细胞对自身抗原谷氨酸脱羧酶65（GAD 65）的反应性与人类和非肥胖糖尿病（NOD）小鼠的疾病发展相关。在这项研究中，我们确定了两个DRB 1 *0401限制性T细胞表位从人类GAD 65，274-286和115-127。这两种肽在表达功能性DRB 1 *0401 MHC II类分子的转基因小鼠中具有免疫原性，但在非转基因同窝仔中不具有免疫原性。抗原呈递细胞（APC）对GAD 65的加工导致形成负载有274-286或115-127个表位的DRB 1 *0401复合物，表明这些天然衍生的表位可以展示在募集到胰岛中的APC上。这两个T细胞表位在有1型糖尿病风险的DRB 1 *0401个体的胰岛中的呈递可以允许肽免疫后调节细胞向胰岛的抗原特异性募集。
The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen-specific immune modulation therapy. In the case of type I diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1 diabetes may allow for antigen-specific recruitment of regulatory cells to the islets following peptide immunization.