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Tumor-associated Neu5Ac-Tn and Neu5Gc-Tn antigens bind to C-type lectin CLEC10A (CD301, MGL)
- Source :
- Glycobiology; Vol 23
- Publication Year :
- 2013
- Publisher :
- Oxford University Press (OUP), 2013.
-
Abstract
- In human tumors, glycoproteins often exhibit abnormal glycosylation patterns, e.g. certain Lewis structures, TF antigen, Tn antigen and/or their sialylated forms, creating additional binding sites for glycoreceptors. In the present study, we have analyzed the carbohydrate specificity of the C-type lectin CLEC10A using glycan profiling by enzyme-linked immunosorbent assay (ELISA). In addition to the known ligands, we show binding to two tumor-associated antigens, namely Neu5Acα2,6-Tn and Neu5Gcα2,6-Tn, with an affinity of CLEC10A in the micromolar range. Detailed analyses of the glycan-lectin interactions were carried out by surface plasmon resonance (SPR) and saturation transfer difference (STD) NMR. CLEC10A binds Neu5Acα2,6-Tn and Neu5Gcα2,6-Tn with dissociation constants of 297 and 80 µM, respectively, as determined by SPR. Comparison of the STD nuclear magnetic resonance (NMR) binding epitopes of Tn and Neu5Acα2,6-Tn revealed a constant binding mode of the N-acetylgalactosamine moiety. This finding is in good agreement with binding studies of CLEC10A transfectomas, which show a well-defined interaction of transmembrane CLEC10A with 6-sialylated-Tn structures. Since both Neu5Acα2,6-Tn and Neu5Gcα2,6-Tn together with the previously known Tn antigen are expressed in human tumors such as mammary carcinoma, the interaction with CLEC10A expressed by macrophages and dendritic cells could be of major functional significance in tumor progression.
- Subjects :
- CLEC10A
Tn antigen
CHO Cells
Biology
Biochemistry
Epitope
03 medical and health sciences
Cricetulus
0302 clinical medicine
Antigen
C-type lectin
Cricetinae
Animals
Humans
Antigens, Tumor-Associated, Carbohydrate
Lectins, C-Type
Binding site
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Lectin
Molecular biology
N-Acetylneuraminic Acid
HEK293 Cells
chemistry
biology.protein
Neuraminic Acids
Glycoprotein
Protein Binding
030215 immunology
Subjects
Details
- ISSN :
- 14602423 and 09596658
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Glycobiology
- Accession number :
- edsair.doi.dedup.....67e63a9d42931ed75fde13ea7978c420