Department of Immunology, University of Colorado Denver School of Medicine, Denver, CO, USA.
Curr Opin Immunol. 2011 Dec;23(6):739-45. doi: 10.1016/j.coi.2011.08.004. Epub 2011 Sep 12.
Pathogenesis of type 1 diabetes (T1D) is mediated by effector T cells and CD4 Th1 and Th17T cells have important roles in this process. While effector function of Th1 cells is well established, because of their inherent plasticity Th17 cells have been more controversial. Th17 cells contribute to pathogenicity, but several studies indicate that Th17 cells transfer disease through conversion to Th1 cells in vivo. CD4T cells are attracted to islets by β-cell antigens which include insulin and the two new autoantigens, chromogranin A and islet amyloid polypeptide, all proteins of the secretory granule. Peptides of insulin and ChgA bind to the NOD class II molecule in an unconventional manner and since autoantigenic peptides may typically bind to MHC with low affinity, it is postulated that post-translational modifications of β-cell peptides could contribute to the interaction between peptides, MHC, and the autoreactive TCR.
1 型糖尿病（T1D）的发病机制是由效应 T 细胞介导的，CD4 Th1 和 Th17T 细胞在这一过程中起着重要作用。虽然 Th1 细胞的效应功能已得到很好的证实，但由于其固有可塑性，Th17 细胞一直存在争议。Th17 细胞有助于致病性，但有几项研究表明，Th17 细胞通过在体内转化为 Th1 细胞来传递疾病。β 细胞抗原包括胰岛素和两种新的自身抗原——嗜铬粒蛋白 A 和胰岛淀粉样多肽，所有这些都是分泌颗粒的蛋白质，将 CD4T 细胞吸引到胰岛。胰岛素和 ChgA 的肽以非传统的方式与 NOD Ⅱ类分子结合，由于自身抗原肽通常与 MHC 结合的亲和力较低，因此推测β细胞肽的翻译后修饰可能有助于肽、MHC 和自身反应性 TCR 之间的相互作用。
