A critical role for sialylation in cryoglobulin activity of murine IgG3 monoclonal antibodies

Autor: Munehiro Nakata, Shuichi Kikuchi, Shozo Izui, Aki Kuroki, Takaaki Funase, Yasuhiro Kuroda
Rok vydání: 2005
Předmět:
Mice
Inbred MRL lpr
medicine.drug_class
Immunology
Molecular Sequence Data
Oligosaccharides
chemical and pharmacologic phenomena
Centrifugation
Mice
Transgenic
ddc:616.07
Galactose/chemistry/metabolism
Monoclonal antibody
complex mixtures
chemistry.chemical_compound
Mice
Cryoglobulin
parasitic diseases
Freezing
medicine
Immunology and Allergy
Sialic Acids/*chemistry/*metabolism
Animals
Chemical Precipitation
Humans
Cryoglobulins
Immunoglobulin G/chemistry/genetics/isolation & purification/*metabolism
chemistry.chemical_classification
biology
Oligosaccharides/chemistry/isolation & purification/metabolism
Chemistry
Autoantibody
Antibodies
Monoclonal
Galactose
Oligosaccharide
Cryoglobulins/antagonists & inhibitors/isolation &
Amino acid
Sialic acid
purification/*metabolism
Biochemistry
Carbohydrate Sequence
Immunoglobulin G
biology.protein
Sialic Acids
Antibody
Antibodies
Monoclonal/chemistry/genetics/*metabolism
Zdroj: Journal of Immunology, Vol. 175, No 2 (2005) pp. 1056-1061
ISSN: 0022-1767
Popis: Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. However, the structural basis of IgG3 cryoprecipitation still remains to be defined. In view of the implication of positively charged amino acid residues present in variable regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb. Comparative oligosaccharide structural analysis of different cryogenic and non-cryogenic IgG3 mAb showed an inverse correlation between the extent of sialylation and cryogenic activity. The inhibitory role of sialylation was further confirmed by the demonstration of enrichment of less and more sialylated IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively, separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid contents of the latter fraction became comparable to those of non-cryogenic IgG3 mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more potent in the inhibition of cryoprecipitation of cryogenic IgG3 mAb. Our results thus suggest that the content of negatively charged sialic acids in oligosaccharide side chains is one of the critical factors to determine IgG3 cryoglobulin activity, along with amino acid sequences of the IgG3 variable regions.
Databáze: OpenAIRE
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