HIPs and HIP-reactive T cells.
HIPs and HIP-reactive T cells.
复制标题
HIP 和 HIP 反应性 T 细胞。
DOI：
10.1111/cei.13335
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发表时间：
2019
影响因子：
4.6
通讯作者：
Delong,T
中科院分区：
文献类型：
--
作者：
Wiles,TA;Delong,T
越来越多的证据表明，杂合胰岛素肽（HIP）作为重要的自身抗原在1型糖尿病（T1D）的发展。胰岛素和其他胰腺β细胞衍生肽之间形成的这些融合肽含有非基因组编码的氨基酸序列，使其成为T1D中自身反应性T细胞的合理靶点。HIP可通过质谱法在人和鼠胰岛中检测到，并被非肥胖糖尿病小鼠中的糖尿病诱导T细胞以及从患有T1D的人器官供体的残余胰岛中分离的T细胞靶向。HIP的发现带来了许多新的挑战，也为研究T1D的发病机制提供了机会。在这里，我们回顾了HIP的最初发现，并描述了最近的研究调查HIP反应性T细胞在糖尿病发展中的作用。我们还讨论了潜在的机制，可能是负责在β细胞中产生HIP，并描述了需要解决的质谱领域，使新的HIP的发现的挑战。在T1D中鉴定这些潜在的疾病驱动抗原是该领域的关键兴趣，因为它可以提供预测，预防和潜在逆转疾病的新工具。
Mounting evidence implicates hybrid insulin peptides (HIPs) as important autoantigens in the development of type 1 diabetes (T1D). These fusion peptides formed between insulin and other pancreatic beta cell-derived peptides contain non-genomically encoded amino acid sequences, making them plausible targets for autoreactive T cells in T1D. HIPs are detectable by mass spectrometry in human and murine islets and are targeted by diabetes-inducing T cells in non-obese diabetic mice as well as by T cells isolated from the residual pancreatic islets of human organ donors with T1D. The discovery of HIPs comes with numerous new challenges, as well as opportunities to study the pathogenesis of T1D. Here we review the original discovery of HIPs and describe recent studies investigating the role of HIP-reactive T cells in the development of diabetes. We also discuss potential mechanisms that may be responsible for the generation of HIPs in beta cells and describe challenges that need to be addressed in the field of mass spectrometry to enable the discovery of new HIPs. The identification of these potentially disease-driving antigens in T1D is of key interest to the field as it may provide new tools to predict, prevent and potentially reverse the disease.