It is still an enigma why T cell autoreactivity in type 1 diabetes targets few beta cell antigens only. Among these, one primary autoantigen is pro(insulin). Autoimmune T cells preferentially recognise three epitopes on the proinsulin molecule, of which the peptide region B:11-23 is the dominant one. Interestingly, the three regions superimpose with binding sites of the chaperone hsp70, the region B:11-23 being the strongest binding one. Absence of an intact core region B:15-17 prevents autoimmune diabetes in NOD as well as binding of hsp70. A role of hsp70 in selecting autoimmune epitopes is supported by the ability of this and other chaperones to deliver bound peptides to MHC class I and II molecules for efficient antigen presentation. Binding of hsp70 to receptors on antigen presenting cells such as TLR4 results in costimulatory signals for T cell activation. Strongest effects are seen for the mixture of hsp70 with the peptide B:11-23. Thus, hsp70 may assist in proinsulin epitope selection and efficient presentation to autoreactive T cells. The concept of chaperone guided immune reactivity may also apply to other autoimmune diseases.

中文翻译：

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伴侣可能导致糖尿病自身免疫集中在独特的（原）胰岛素肽上。

为什么1型糖尿病患者的T细胞自身反应性仅靶向很少的β细胞抗原，仍是一个谜。其中，一种主要的自身抗原是原胰岛素。自身免疫性T细胞优先识别胰岛素原分子上的三个表位，其中肽区B：11-23是主要表位。有趣的是，这三个区域与伴侣hsp70的结合位点重叠，区域B：11-23是最强的结合位点。缺失完整的核心区域B：15-17可防止NOD中的自身免疫性糖尿病以及hsp70的结合。hsp70在选择自身免疫抗原决定簇中的作用得到了这种和其他分子伴侣将结合的肽递送至MHC I类和II类分子以进行有效抗原呈递的能力的支持。hsp70与抗原呈递细胞（例如TLR4）上的受体结合会导致T细胞活化的共刺激信号。对于hsp70与肽B：11-23的混合物，观察到最强的作用。因此，hsp70可能有助于胰岛素原表位的选择和向自身反应性T细胞的有效呈递。伴侣伴侣指导的免疫反应性的概念也可适用于其他自身免疫性疾病。