Briand Jean-Paul, Schall Nicolas, Muller Sylviane
Immunopathology and Therapeutic Chemistry, CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
Methods Mol Biol. 2014;1134:173-92. doi: 10.1007/978-1-4939-0326-9_13.
Synthetic peptides are attracting increasing attention as therapeutics. Despite their potential, however, only a few selected peptides have been able to enter in clinical trials for chronic autoimmune diseases and systemic lupus erythematosus (SLE) in particular. Here, we describe and discuss a series of assays, which may help in characterizing valuable candidate peptides that were applied in our laboratory to develop the lupus P140 peptide program. The different steps of selection include the choice of the initial autoantigen, the design, synthesis and purification of peptides, their preliminary screen by measuring cytokines produced ex vivo by T cells and their binding to major histocompatibility complex class II (MHCII) molecules, their capacity to lower peripheral cell hyperproliferation in lupus-prone MRL/lpr mice, and, as a final step, their ability to slow down the development of lupus disease in model animals.
合成肽作为治疗药物正受到越来越多的关注。然而，尽管它们具有潜力，但只有少数经过挑选的肽能够进入慢性自身免疫性疾病尤其是系统性红斑狼疮（SLE）的临床试验。在此，我们描述并讨论了一系列检测方法，这些方法可能有助于鉴定有价值的候选肽，我们实验室曾应用这些方法来开展狼疮P140肽项目。选择的不同步骤包括初始自身抗原的选择、肽的设计、合成与纯化、通过检测T细胞体外产生的细胞因子及其与主要组织相容性复合体II类（MHCII）分子的结合进行初步筛选、它们降低狼疮易感MRL/lpr小鼠外周细胞过度增殖的能力，以及作为最后一步，它们减缓模型动物狼疮疾病发展的能力。
