Galactose-Deficient IgA1-Specific Antibody Recognizes GalNAc-Modified Unique Epitope on Hinge Region of IgA1
| Autor: | Kohei Yamasaki, Junichi Yasutake, Yamazaki Yuji, Yusuke Suzuki, Hitoshi Suzuki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Glycosylation medicine.drug_class Immunology 030232 urology & nephrology Peptide Monoclonal antibody Epitope 03 medical and health sciences chemistry.chemical_compound Epitopes 0302 clinical medicine fluids and secretions stomatognathic system Antibody Specificity parasitic diseases medicine Immunology and Allergy Moiety Humans chemistry.chemical_classification epitope Ligand binding assay Antibodies Monoclonal Galactose Glomerulonephritis IGA Original Articles Molecular biology Immunoglobulin A carbohydrates (lipids) Specific antibody 030104 developmental biology chemistry galactose-deficient IgA1 monoclonal antibody lipids (amino acids peptides and proteins) ELISA Hinge region |
| Zdroj: | Monoclonal Antibodies in Immunodiagnosis and Immunotherapy |
| ISSN: | 2167-9436 |
| Popis: | Galactose-deficient IgA1 (Gd-IgA1) that exposes GalNAc or sialylated GalNAc has been shown to be associated with disease activity of IgA nephropathy (IgAN). In a previous report, we established an enzyme-linked immunosorbent assay that measures human Gd-IgA1 using a specific monoclonal antibody KM55 (KM55 mAb), and showed that patients with IgAN contain a higher level of serum Gd-IgA1 than other types of renal diseases. Recently, we also found that the KM55 mAb specifically recognized the glomerular-deposited Gd-IgA1 in renal biopsy. In this study, we aimed to analyze the epitope of KM55 mAb using synthesized peptides corresponding to the hinge region of IgA1 with GalNAc moiety on putative glycosylated Ser/Thr residues, which are Thr225, Thr228, Ser230, Ser232, and Thr236. Binding analysis to single GalNAc-modified hinge region peptide of IgA1 showed that Thr225 with GalNAc is required for recognition of KM55. PST(GalNAC)PP motif was required for KM55 mAb to recognize hinge region peptide of IgA1 which is shown by binding assay with deletion peptide. This result was confirmed by binding of KM55 mAb against peptide with GalNAc at Thr233, which resulted in containing another PST(GalNAC)PP motif. Taken together, we concluded that the epitope of Gd-IgA1-specific KM55 mAb is PST(GalNAc)PP motif. |
| Databáze: | OpenAIRE |
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