A SHORT SEQUENCE, WITHIN THE AMINO-ACID TANDEM REPEAT OF A CANCER-ASSOCIATED MUCIN, CONTAINS IMMUNODOMINANT EPITOPES
A SHORT SEQUENCE, WITHIN THE AMINO-ACID TANDEM REPEAT OF A CANCER-ASSOCIATED MUCIN, CONTAINS IMMUNODOMINANT EPITOPES
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DOI：
10.1002/ijc.2910440423
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发表时间：
1989-10-15
影响因子：
6.4
通讯作者：
DUHIG, T
中科院分区：
文献类型：
--
作者：
BURCHELL, J;TAYLORPAPADIMITRIOU, J;DUHIG, T
多态性上皮粘蛋白 (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 个氨基酸串联重复组成的大结构域，该结构域具有高度免疫显性，因为许多与该分子反应的抗体识别该区域内的表位。使用重叠的肽八聚体，我们精确地绘制了 4 个 MAb 与串联重复反应的表位，其中包括 SM-3，它显示出增强的肿瘤特异性。我们报道 SM-3 表位的核心对应于连续氨基酸序列 Pro-Asp-Thr-Arg-Pro。我们还表明，其他 3 种抗体识别的表位（显示出与正常和恶性组织的反应性）映射到串联重复的该区域内。然而，这些表位都不包含 SM-3 决定簇氨基末端的脯氨酸。这些结果与以下观点一致：在与癌症相关的粘蛋白中，碳水化合物侧链的过早终止导致 SM-3 表位的暴露。
The polymorphic epitehlial 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.