修饰性肽配体的作用机制、应用及筛选进展

Advances in the study of molecular mechanisms,applications and screening for altered peptide ligand

修饰性肽配体是在抗原表位的基础上对表位进行氨基酸改造形成的具有免疫调节活性的短肽,已经在治疗自身免疫疾病、恶性肿瘤和病毒感染等疾病方面显示出良好的应用前景。一方面,修饰性肽配体可通过影响天然抗原表位、主要组织相容性复合体和T细胞受体形成的三分子结构发挥特异性免疫调节作用;另一方面,修饰性肽配体还可通过改变抗原呈递细胞内信号、旁路抑制和激发异源性免疫反应等机制发挥治疗作用。结合使用噬菌体展示技术对肽库进行筛选,可获得大量高特异性和高亲和力修饰性肽配体。修饰性肽配体作为潜在抗原特异性药物的重要来源正在受到广泛关注。

Altered peptide ligand （APL）, a short peptide with immune regulatory activity and substitutions of a single or multiple amino acids in an antigenic peptide, has shown potential therapeutic effect on autoimmune disease, tumor and virus infection. APL regulates immune responses by interfering the interaction between the major histocompatibility complex （MHC）, antigenic peptide and T cell receptor （TCR）, or by regulating the intracellular signaling of antigen presenting cells, bystander suppression and inducing heterogenous immune responses. High-specific and high-affinity APL screened from peptide laboratory by phage display, has a potential to be a new resource for drug with antigen specificity.