Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen.
Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen.
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发表时间：
1995-08
期刊：
影响因子：
11.2
通讯作者：
S. Zhang;L. A. Walberg;S. Ogata;S. Itzkowitz;R. Koganty;M. Reddish;S. Gandhi;B. M. Longenecker;K. Lloyd;P. Livingston
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作者：
S. Zhang;L. A. Walberg;S. Ogata;S. Itzkowitz;R. Koganty;M. Reddish;S. Gandhi;B. M. Longenecker;K. Lloyd;P. Livingston
Sialyl Tn （sTn）是一种在大多数人类腺癌中表达的黏液相关碳水化合物抗原。确定被抗体识别的肿瘤细胞表面sTn的结构，对于理解sTn反应性单克隆抗体的癌细胞特异性基础、开发更有效的单克隆抗体以及设计针对sTn的癌症疫苗具有重要意义。在本研究中，我们比较了合成的sTn单糖表位和3个sTn表位通过丝氨酸共价连接到keyhole帽贝血青素[KLH]的簇[sTn(C)]的免疫原性；sTn-KLH和sTn(C)-KLH]。用这些新糖蛋白免疫小鼠血清和一组sTn反应单抗分析细胞表面sTn结构。sTn-KLH免疫小鼠血清与sTn-人血清白蛋白（HSA）有直接和抑制反应，但与sTn(C)-HSA有弱反应，而sTn(C)-KLH免疫小鼠血清与sTn(C)-HSA有反应，但与sTn-HSA无反应。抗sTn和抗sTn(C)血清与羊颌下粘蛋白（sTn的天然来源）和sTn阳性的人肿瘤细胞系LS-C均有反应，但与sTn阴性的LS-B细胞无反应。对于sTn反应性单克隆抗体，B72.3只与聚集的sTn反应，而B195.3R11单克隆抗体优先与非聚集的sTn反应。单克隆抗体TKH2、B239.1和CC49的结果不太清楚，尽管它们与聚集性sTn的反应比与非聚集性sTn的反应更强烈。这些结果表明，sTn在肿瘤细胞表面至少以两种截然不同的构型被识别，即集群和非集群阵列。
Sialyl Tn (sTn) is a mucin-associated carbohydrate antigen expressed in most types of human adenocarcinoma. Defining the configuration of tumor cell surface sTn recognized by antibodies is important for understanding the basis for the cancer cell specificity of sTn-reactive mAbs, for the development of more effective mAbs, and for designing cancer vaccines against sTn. In this study, we compared the immunogenicity of synthetic single sTn disaccharide epitopes and clusters [sTn(C)] of 3 sTn epitopes covalently linked via serine to keyhole limpet hemocyanin [KLH; sTn-KLH and sTn(C)-KLH, respectively]. The cell surface sTn configurations were analyzed with the use of sera from mice immunized with these neoglycoproteins and a panel of sTn-reactive mAb. Sera from mice immunized with sTn-KLH reacted in direct and inhibition assays with sTn-human serum albumin (HSA) but only weakly with sTn(C)-HSA, whereas sera from mice immunized with sTn(C)-KLH reacted with sTn(C)-HSA but not with sTn-HSA. Both anti-sTn and anti-sTn(C) sera reacted with ovine submaxillary mucin (a natural source of sTn) and with sTn-positive human tumor cell line LS-C but not with sTn-negative LS-B cells. With regard to the sTn-reactive mAbs, B72.3 reacted exclusively with clustered sTn, whereas mAb B195.3R11 reacted preferentially with unclustered sTn. Results with mAbs TKH2, B239.1, and CC49 were less clear, although all reacted more strongly with clustered sTn than with unclustered sTn. These results suggest that sTn is recognized at the tumor cell surface in at least two quite distinct configurations, as clustered and nonclustered arrays.