Hiemstra H S, van Veelen P A, Schloot N C, Geluk A, van Meijgaarden K E, Willemen S J, Leunissen J A, Benckhuijsen W E, Amons R, de Vries R R, Roep B O, Ottenhoff T H, Drijfhout J W
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
J Immunol. 1998 Oct 15;161(8):4078-82.
Progress has recently been made in the use of synthetic peptide libraries for the identification of T cell-stimulating ligands. T cell epitopes identified from synthetic libraries are mimics of natural epitopes. Here we show how the mimicry epitopes obtained from synthetic peptide libraries enable unambiguous identification of natural T cell Ags. Synthetic peptide libraries were screened with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two cases, database homology searches with mimicry epitopes isolated from a dedicated synthetic peptide library allowed immediate identification of the natural antigenic protein. In two other cases, an amino acid pattern that reflected the epitope requirements of the T cell was determined by substitution and omission mixture analysis. Subsequently, the natural Ag was identified from databases using this refined pattern. This approach opens new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches described thus far.
近期在利用合成肽库鉴定T细胞刺激配体方面取得了进展。从合成库中鉴定出的T细胞表位是天然表位的模拟物。在此我们展示了从合成肽库获得的模拟表位如何能够明确鉴定天然T细胞抗原。用结核分枝杆菌反应性和自身反应性T细胞克隆筛选合成肽库。在两个案例中，对从专门合成肽库分离出的模拟表位进行数据库同源性搜索，可立即鉴定出天然抗原蛋白。在另外两个案例中，通过取代和缺失混合分析确定了反映T细胞表位需求的氨基酸模式。随后，利用这种优化模式从数据库中鉴定出天然抗原。这种方法为快速可靠地定义抗原开辟了新视角，是目前所描述的生化和遗传方法的可行替代方案。
