The association of autoimmune diseases with particular allellic products of the class-II major histocompatibility complex (MHCII) region implicates the presentation of the offending self-antigens to T cells. Because antigen-presenting cells are tolerogenic when they encounter an antigen under non-inflammatory conditions, the manipulation of antigen presentation may induce antigen-specific tolerance. Here, we show that, in mouse models of experimental autoimmune encephalomyelitis, type 1 diabetes and rheumatoid arthritis, the systemic administration of a single dose of nanobodies that recognize MHCII molecules and conjugated to the relevant self-antigen under non-inflammatory conditions confers long-lasting protection against these diseases. Moreover, co-administration of a nanobody–antigen adduct and the glucocorticoid dexamethasone, conjugated to the nanobody via a cleavable linker, halted the progression of established experimental autoimmune encephalomyelitis in symptomatic mice and alleviated their symptoms. This approach may represent a means of treating autoimmune conditions.

自身免疫性疾病与 II 类主要组织相容性复合体 (MHCII) 区域的特定等位基因产物的关联暗示了攻击性自身抗原对 T 细胞的呈递。由于抗原呈递细胞在非炎症条件下遇到抗原时会产生耐受性，因此抗原呈递的操作可能会诱导抗原特异性耐受。在这里，我们表明，在实验性自身免疫性脑脊髓炎、1 型糖尿病和类风湿性关节炎的小鼠模型中，在非炎症条件下全身施用单剂量的识别 MHCII 分子并与相关自身抗原结合的纳米抗体可长期对这些疾病的持久保护。此外，纳米抗体-抗原加合物和糖皮质激素地塞米松的共同给药，通过可切割的接头与纳米抗体结合，阻止了有症状小鼠中已建立的实验性自身免疫性脑脊髓炎的进展并减轻了它们的症状。这种方法可能代表一种治疗自身免疫病症的方法。