Burchell J, Taylor-Papadimitriou J, Boshell M, Gendler S, Duhig T
Imperial Cancer Research Fund, London, UK.
Int J Cancer. 1989 Oct 15;44(4):691-6. doi: 10.1002/ijc.2910440423.
The polymorphic epithelial mucin (PEM) appears to be the target molecule for many monoclonal antibodies (MAbs) which react with tumour-associated and epithelium-specific antigens. PEM contains a large domain made up of 20 amino-acid tandem repeats which are highly immunodominant as many of the antibodies reactive with this molecule recognize epitopes within this area. Using overlapping peptide octamers, we have precisely mapped the epitopes of 4 MAbs reactive with the tandem repeats including one, SM-3, which shows enhanced tumour specificity. We report that the core of the SM-3 epitope corresponds to the continuous amino acid sequence Pro-Asp-Thr-Arg-Pro. We also show that the epitopes recognized by 3 other antibodies, which show reactivity with normal and malignant tissues, map to within this area of the tandem repeat. However, none of these epitopes contain the proline found at the amino end of the SM-3 determinant. These results are consistent with the idea that, in the cancer-associated mucin, premature termination of the carbohydrate side-chains results in the exposure of the SM-3 epitope.
多形上皮黏蛋白（PEM）似乎是许多单克隆抗体（MAb）的靶分子，这些单克隆抗体可与肿瘤相关抗原和上皮特异性抗原发生反应。PEM包含一个由20个氨基酸串联重复序列组成的大结构域，由于许多与该分子反应的抗体识别该区域内的表位，所以该区域具有高度免疫显性。利用重叠的八聚体肽，我们精确地绘制了4种与串联重复序列反应的单克隆抗体的表位图谱，其中包括一种显示出增强的肿瘤特异性的单克隆抗体SM-3。我们报告SM-3表位的核心对应于连续的氨基酸序列脯氨酸-天冬氨酸-苏氨酸-精氨酸-脯氨酸。我们还表明，另外3种与正常组织和恶性组织都有反应的抗体所识别的表位定位于串联重复序列的这个区域内。然而，这些表位中没有一个含有在SM-3决定簇氨基末端发现的脯氨酸。这些结果与以下观点一致：在癌症相关黏蛋白中，碳水化合物侧链的过早终止导致了SM-3表位的暴露。
