Predominantly recognized proinsulin T helper cell epitopes in individuals with and without islet cell autoimmunity
Predominantly recognized proinsulin T helper cell epitopes in individuals with and without islet cell autoimmunity
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DOI：
10.1006/jaut.2001.0566
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发表时间：
2002-02-01
影响因子：
12.8
通讯作者：
Ziegler, AG
中科院分区：
文献类型：
--
作者：
Durinovic-Belló, I;Boehm, BO;Ziegler, AG
抗体对胰岛素及其前体胰岛素原的反应与1型糖尿病（T1D）的风险增加有关，尽管对T细胞对该分子的反应性知之甚少。本研究从外周血单核细胞（PBMC）中富集了体内引物CD45RO（+）记忆T辅助细胞（Th），并分析了它们对8种重叠的胰岛素原肽和蛋白质的反应性。研究HLA-DRB1*04、DQB1*0302等位基因高危人群：具有胰岛细胞自身免疫体液标志物（自身抗体阳性，Ab +, n = 11）的T1D患者亲属、T1D患者（n = 8）和健康对照（n = 16）。在所有测试个体中，最常识别的胰岛素原表位是C肽(C) 18-A链(A)1。在Ab+亲缘关系中，观察到对该表位和原胰岛素的两个额外部分，B链(B) 11-C24和C28-A21的反应。在已经接受胰岛素治疗的T1D患者中，对肽B20-C4和整个胰岛素分子的反应占主导地位。我们的研究结果表明，在具有高危HLA等位基因的个体中，自发记忆细胞对胰岛素原的反应主要指向一个表位，该表位映射到中心的c肽区域。在具有胰岛细胞自身免疫体液标志物的个体和T1D患者中，观察到对不同胰岛素原区域的扩散反应。(C) 2002 Elsevier Science Ltd.
Antibody response to insulin and to its precursor ProInsulin is associated with increased risk for type 1 diabetes (T1D), though little is known about T cell reactivity to this molecule. In the present study from peripheral blood mononuclear cells (PBMC), in vivo primed CD45RO(+) memory T helper (Th) cells were enriched and their reactivity to eight overlapping ProInsulin peptides and to protein was analyzed. Individuals with high risk HLA-DRB1*04, DQB1*0302 alleles were investigated: relatives of patients with T1D having humoral markers of islet cell autoimmunity (autoantibody positive, Ab +; n = 11), patients with T1D (n = 8), and healthy control individuals (n = 16). The ProInsulin epitope which was most frequently recognized in all the tested individuals was C-peptide (C) 18-A-chain (A)1. In Ab+ relatives the responses to this epitope and to two additional parts of the ProInsulin, B-chain (B) 11-C24 and C28-A21, was observed. In T1D patients who have already been treated with insulin, response to peptide B20-C4 and to the entire insulin molecule predominates. Our findings suggest that the spontaneous memory Th cell response to ProInsulin in individuals with high risk HLA alleles is predominantly directed to one epitope which maps to the central, C-peptide region. In individuals with humoral markers of islet cell autoimmunity and in patients with T1D, spread response to distinct ProInsulin regions was observed. (C) 2002 Elsevier Science Ltd.