Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65)
Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65)
复制标题
DOI：
10.1073/pnas.98.4.1763
复制
发表时间：
2001-02-13
影响因子：
11.1
通讯作者：
Nepom, BS
中科院分区：
文献类型：
--
作者：
Nepom, GT;Lippolis, JD;Nepom, BS
T细胞对自身抗原的识别对于胰岛细胞的进行性免疫介导的破坏至关重要，这导致自身免疫性糖尿病。我们确定了一个自然提出的自身抗原从人胰岛抗原谷氨酸脱羧酶，65 kDa亚型（GAD 65），通过使用色谱和质谱结合的肽与I型糖尿病（胰岛素依赖型糖尿病，IDDM）相关的HLA-DR 4分子。包含该表位刺激的GAD 65特异性T细胞的肽来自糖尿病患者和发展为IDDM的高风险的DR 4阳性个体，T细胞应答被含有单个氨基酸修饰的改变的肽配体拮抗。GAD 65表位识别的这种直接识别和操作提供了一种剖析IDDM中复杂的CD 4（+）T细胞反应的方法。
T cell recognition of autoantigens is critical to progressive immune-mediated destruction of islet cells, which leads to autoimmune diabetes. We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM, T cell responses were antagonized by altered peptide ligands containing single amino acid modifications. This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM.