细菌鞭毛蛋白在Treg表位肽自身免疫性风湿病治疗中的应用前景

Application potential of bacterial flagellin in treatment of autoimmune rheumatic diseases with Treg epitope peptides

用调节性T细胞(Treg)表位肽进行免疫、激发和诱导表位肽特异的Treg细胞,抑制过强的自身免疫应答,从而建立起新的免疫稳态,是一个很有前景的自身免疫性风湿病的治疗方案,然而小分子的表位肽通常很难在体内有效激发出表位肽特异的免疫应答。细菌鞭毛蛋白是固有免疫系统的一种激动剂,在作为偶联载体时对偶联的抗原有极强的佐剂作用,在特定情况下能够激发和诱导Treg细胞。因此,如果将Treg细胞表位肽与细菌鞭毛蛋白共价偶联,偶联体应可通过鞭毛蛋白本身的作用,以及鞭毛蛋白对Treg细胞表位肽的佐剂作用,有效增强基于Treg细胞的免疫应答,从而增强对自身免疫性风湿病的免疫治疗效果。

Immunization with regulatory T cell (Treg) epitope peptides to activate and induce Tregs, by which to suppress pathological autoimmune responses and reconstitute a new homeostasis, is a promising therapeutic regimen for autoimmune rheumatic diseases. However, it is usually hard to induce potent peptide-specific immune responses in vivo with small molecular peptides. Bacterial flagellin is one of the agonists triggering innate immune responses. When used as carrier, it shows strong adjuvant activity to its conjugated antigens. In some particular situations, bacterial flagellin can also activate and induce Tregs. Thus if Treg epitope peptides are covalently conjugated to a bacterial flagellin, the conjugates should be able to effectively enhance the Treg-based immune responses via flagellin itself and the adjuvanticity of flagellin to Treg epitope peptides, and thereby enhance the immunotherapeutic effects on autoimmune rheumatic diseases.