Wiesmüller K H, Fleckenstein B, Jung G
EMC microcollections GmbH, Tübingen, Germany.
Biol Chem. 2001 Apr;382(4):571-9. doi: 10.1515/BC.2001.070.
Synthetic immunogens, containing built-in adjuvanticity, B cell, T helper cell and CTL epitopes or mimotopes, are ideal and invaluable tools to study the immune response with respect to antigen processing and presentation. This serves as a basis for the development of complete and minimal vaccines which do not need large carrier proteins, further adjuvants, liposome formulations or other delivery systems. Combinatorial peptide libraries, either completely random or characterized by one or several defined positions, are useful tools for the identification of the critical features of B cell epitopes and of MHC class I and class II binding natural and synthetic epitopes. The complete activity pattern of an O/Xn library with hundreds of peptide collections, each made up from billions of different peptides, represents the ranking of amino acid residues mediating contact to the target proteins of the immune system. Combinatorial libraries support the design of peptides applicable in vaccination against infectious agents as well as therapeutic tumour vaccines. Using the principle of lipopeptide vaccines, strong humoral and cellular immune responses could be elicited. The lipopeptide vaccines are heat-stable, non-toxic, fully biodegradable and can be prepared on the basis of minimized epitopes by modern methods of multiple peptide synthesis. The lipopeptides activate the antigen-presenting macrophages and B cells and have been recently shown to stimulate innate immunity by specific interaction with receptors of the Toll family.
合成免疫原含有内在佐剂活性、B细胞、辅助性T细胞和细胞毒性T淋巴细胞表位或模拟表位,是研究抗原加工和呈递免疫反应的理想且极有价值的工具。这为开发无需大型载体蛋白、额外佐剂、脂质体制剂或其他递送系统的全效和简化疫苗奠定了基础。完全随机或由一个或几个特定位置表征的组合肽文库,是鉴定B细胞表位以及MHCⅠ类和Ⅱ类结合天然和合成表位关键特征的有用工具。一个拥有数百个肽库的O/Xn文库的完整活性模式,每个肽库由数十亿种不同肽组成,代表了介导与免疫系统靶蛋白接触的氨基酸残基的排名。组合文库有助于设计适用于针对感染因子的疫苗接种以及治疗性肿瘤疫苗的肽。利用脂肽疫苗的原理,可引发强烈的体液免疫和细胞免疫反应。脂肽疫苗具有热稳定性、无毒、完全可生物降解,并且可以通过现代多肽合成方法基于最小化表位来制备。脂肽可激活抗原呈递巨噬细胞和B细胞,最近还显示可通过与Toll家族受体的特异性相互作用来刺激先天免疫。