Manimala Joseph C, Li Zhitao, Jain Amit, VedBrat Sharanjeet, Gildersleeve Jeffrey C
Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI-Frederick, 376 Boyles Street, Building 376, Room109, Frederick, MD 21702, USA.
Chembiochem. 2005 Dec;6(12):2229-41. doi: 10.1002/cbic.200500165.
The Tn antigen is a carbohydrate antigen expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV. It has been evaluated extensively as a potential diagnostic marker and several Tn-based vaccines are in clinical trials. Based on discrepancies in the literature regarding Tn expression, we began to question whether antibodies and lectins used routinely to detect the Tn antigen were providing accurate information. To investigate this possibility, a carbohydrate microarray and a highly sensitive assay were developed and three frequently used Tn receptors (HBTn1, Bric111, and VVL-B4) were evaluated. Carbohydrate-array analysis revealed unexpected cross-reactivity with other human carbohydrate epitopes. VVL-B4 bound the Tn antigen, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. Bric111 bound the Tn antigen, blood group A, GalNAcalpha1-6Gal, and GalNAcalpha1-3Gal. HBTn1 showed the best selectivity, but still displayed moderate binding to blood group A. Implications for the development of Tn-based diagnostics and vaccines are discussed.
Tn抗原是一种碳水化合物抗原，在大多数癌组织、胚胎发育过程、致病寄生虫以及HIV上表达。它作为一种潜在的诊断标志物已得到广泛评估，并且几种基于Tn的疫苗正处于临床试验阶段。基于文献中关于Tn表达的差异，我们开始质疑常规用于检测Tn抗原的抗体和凝集素是否能提供准确信息。为了研究这种可能性，我们开发了一种碳水化合物微阵列和一种高灵敏度检测方法，并对三种常用的Tn受体（HBTn1、Bric111和VVL-B4）进行了评估。碳水化合物阵列分析揭示了与其他人类碳水化合物表位的意外交叉反应性。VVL-B4能结合Tn抗原、GalNAcalpha1-6Gal和GalNAcalpha1-3Gal。Bric111能结合Tn抗原、血型A、GalNAcalpha1-6Gal和GalNAcalpha1-3Gal。HBTn1表现出最佳的选择性，但仍与血型A有适度结合。本文讨论了其对基于Tn的诊断方法和疫苗开发的影响。
