Bixler G S, Atassi M Z
J Immunogenet. 1984 Jun-Aug;11(3-4):245-50. doi: 10.1111/j.1744-313x.1984.tb01060.x.
In previous studies from this laboratory the antigenic sites of lysozyme were found to be composed of spatially adjacent surface residues that are mostly distant in sequence (i.e. discontinuous sites). For synthetic mimicking of the sites, we introduced the concept of 'surface-simulation' synthesis by which the binding site residues are linked directly via peptide bonds with appropriate spacing and directionality into a single peptide which does not exist in the protein but mimics a surface region of it. In the present report T cell recognition of the surface-simulation synthetic antigenic sites has been explored in a mouse strain, B10.BR, that is a high responder to lysozyme. The discontinuous antigenic sites of lysozyme also had the capacity to stimulate proliferation of T cells driven by native lysozyme in long-term cultures. Thus, in addition to the four continuous T sites that we have recently reported, T cell recognition of lysozyme also involves discontinuous sites. This is the first clear demonstration that, contrary to a long-held impression, T cell recognition is not restricted only to sequence features, but can also be directed to protein discontinuous surface areas of high conformational dependency.
在本实验室之前的研究中，发现溶菌酶的抗原位点由空间上相邻但在序列上大多相隔较远的表面残基组成（即不连续位点）。为了对这些位点进行合成模拟，我们引入了“表面模拟”合成的概念，通过该方法，结合位点残基以适当的间距和方向性通过肽键直接连接成一个在蛋白质中不存在但模拟其表面区域的单一肽段。在本报告中，我们在对溶菌酶反应强烈的小鼠品系B10.BR中探索了表面模拟合成抗原位点的T细胞识别。溶菌酶的不连续抗原位点在长期培养中也具有刺激由天然溶菌酶驱动的T细胞增殖的能力。因此，除了我们最近报道的四个连续T位点外，溶菌酶的T细胞识别还涉及不连续位点。这首次明确证明，与长期以来的观点相反，T细胞识别不仅限于序列特征，还可以针对具有高度构象依赖性的蛋白质不连续表面区域。
