At present, there is no cure for type 1A diabetes (T1D), a T cell-mediated autoimmune disease. Monoclonal antibodies (mAbs) are used to treat a wide number of diseases. For treating T1D, mAbs that target major immune cell subsets show considerable promise, but so far, when used at doses that do not cause unacceptable adverse reactions, have only been able to delay, but not prevent, disease progression. As a potentially safer alternative or adjunct, we have been investigating the utility of mAbs targeting defined peptide‒major histocompatibility complex (MHC) II complexes that are the ligands for disease-relevant CD4⁺ T cells. Alleles within the MHC class II locus confer the greatest genetic risk for T1D, and activation of pathogenic CD4⁺ T cells by antigen-presenting cells (APCs) expressing these ligands is central to disease etiology. Consequently, selective disruption of these critical interactions should arrest autoimmunity without causing global immunosuppression. Here, we review studies using an mAb targeting a key pathogenic epitope from insulin to treat a spontaneous mouse model of T1D and discuss the translational potential of therapies based on this approach.

中文翻译：

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针对致病性肽-MHC 复合物的自身免疫性糖尿病的免疫疗法。

目前，1A 型糖尿病（T1D）尚无治愈方法，这是一种 T 细胞介导的自身免疫性疾病。单克隆抗体 (mAb) 用于治疗多种疾病。对于治疗 T1D，针对主要免疫细胞亚群的单克隆抗体显示出相当大的前景，但到目前为止，当以不会引起不可接受的不良反应的剂量使用时，只能延缓疾病进展，而不能预防疾病进展。作为一种可能更安全的替代方案或辅助手段，我们一直在研究针对特定肽主要组织相容性复合物 (MHC) II 复合物（疾病相关 CD4 + T 细胞的配体）的 mAb 的^效用。MHC II 类基因座内的等位基因赋予 T1D 最大的遗传风险，表达这些配体的抗原呈递细胞 (APC)激活致病性 CD4 ^{+ T 细胞是疾病病因学的核心。}因此，选择性破坏这些关键相互作用应该可以阻止自身免疫，而不会引起整体免疫抑制。在这里，我们回顾了使用针对胰岛素关键致病表位的单克隆抗体治疗自发性 T1D 小鼠模型的研究，并讨论了基于这种方法的治疗的转化潜力。