Carbohydrate array analysis of anti-Tn antibodies and lectins reveals unexpected specificities: Implications for diagnostic and vaccine development

被引:91
作者
Manimala, JC
Li, ZT
Jain, A
VedBrat, S
Gildersleeve, JC
机构
[1] NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA
[2] KamTek Inc, Gaithersburg, MD 20879 USA
关键词
carbohydrates; glycoconjugates; glycosylation; microarrays; Tn antigen;
D O I
10.1002/cbic.200500165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. WL-B4 bound the Tn antigen, GalNAc alpha l-6Gal, and GalNAc alpha 1-3Gal. Bric111 bound the Tn antigen, blood group A GalNAc alpha 1-6Gal, and GalNAc alpha 1-3Gal. 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.
引用
收藏
页码:2229 / 2241
页数:13
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