Identification of immunogenic epitopes of GAD 65 presented by A(g7) in non-obese diabetic mice
Identification of immunogenic epitopes of GAD 65 presented by A(g7) in non-obese diabetic mice
复制标题
DOI：
10.1007/s002510050238
复制
发表时间：
1997-01-01
期刊：
影响因子：
3.2
通讯作者：
McDevitt, HO
中科院分区：
文献类型：
--
作者：
Chao, CC;McDevitt, HO
自身抗原谷氨酸脱羧酶65 （GAD 65）被认为是胰岛素依赖型糖尿病（IDDM）的重要靶抗原，因为观察到年龄相关的自发耐受性破坏，并且在人类和NOD小鼠中已经报道了细胞介导和自身抗体免疫反应。我们试图鉴定GAD 65的免疫原性表位，它是由I型糖尿病易感等位基因（A(g7)）呈递给T细胞的，使用重叠的15-mer合成肽跨越该蛋白的整个序列。通过筛选GAD 65免疫NOD小鼠产生的t细胞杂交瘤，鉴定出4个表位（p206-220, p221-235, p286-300, p571-585）。这些免疫原性表位与先前在NOD小鼠中报道的GAD 65的t细胞表位无关。在gad65氨基酸序列中，206-220和221-235是本研究中发现的两个最主要的t细胞表位。应答GAD 65的T细胞杂交瘤分别有63%和25%对p206-220和p221-235有反应。其余两种多肽（p286-300, p571-585）在t细胞应答中较少占主导地位。GAD 65a （g7）表位全谱的鉴定将进一步研究该自身抗原在IDDM发病机制中的作用。
The autoantigen glutamic acid decarboxylase 65 (GAD 65) is believed to be an important target antigen in insulin-dependent diabetes mellitus (IDDM), since an age-related spontaneous breakdown in tolerance is observed, and cell-mediated and autoantibody immune responses have been reported in humans and NOD mice. We sought to identify immunogenic epitopes of GAD 65 which are presented to T cells by the type I diabetes susceptibility allele (A(g7)), using overlapping 15-mer synthetic peptides spanning the entire sequence of this protein. Four epitopes (p206-220, p221-235, p286-300, p571-585) were identified by screening a panel of T-cell hybridomas generated from GAD 65-immunized NOD mice. These immunogenic epitopes are unrelated to the previously described T-cell epitopes of GAD 65 reported in NOD mice. Of the GAD 65 amino acid sequence, 206-220 and 221-235 are the two most dominant T-cell epitopes identified in this study. Sixty-three percent and 25% of GAD 65-responding T cell hybridomas react to p206-220 and p221-235, respectively. The remaining two peptides (p286-300, p571-585) are less dominant T-cell responses. The identification of the whole spectrum of GAD 65 A(g7) epitopes should further the investigation of the role of this autoantigen in the pathogenesis of IDDM.