Human Natural Antibodies Recognizing Glycan Galß1-3GlcNAc (LeC).
Int J Mol Sci
; 21(18)2020 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-32899593
ABSTRACT
The level of human natural antibodies of immunoglobulin M isotype against LeC in patients with breast cancer is lower than in healthy women. The epitope specificity of these antibodies has been characterized using a printed glycan array and enzyme-linked immunosorbent assay (ELISA), the antibodies being isolated from donors' blood using LeC-Sepharose (LeC is Galß1-3GlcNAcß). The isolated antibodies recognize the disaccharide but do not bind to glycans terminated with LeC, which implies the impossibility of binding to regular glycoproteins of non-malignant cells. The avidity (as dissociation constant value) of antibodies probed with a multivalent disaccharide is 10-9 M; the nanomolar level indicates that the concentration is sufficient for physiological binding to the cognate antigen. Testing of several breast cancer cell lines showed the strongest binding to ZR 75-1. Interestingly, only 7% of the cells were positive in a monolayer with a low density, increasing up to 96% at highest density. The enhanced interaction (instead of the expected inhibition) of antibodies with ZR 75-1 cells in the presence of Galß1-3GlcNAcß disaccharide, indicates that the target epitope of anti-LeC antibodies is a molecular pattern with a carbohydrate constituent rather than a glycan.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dissacarídeos
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Galactanos
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Epitopos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Federação Russa