[The structure of carbohydrate chains of human IgG4-paraproteins differing in the ability to bind cell receptors]

Area of Science:

• Immunology
• Glycobiology
• Biochemistry

Context:

• Human immunoglobulin G4 (IgG4) paraproteins exhibit functional heterogeneity.
• Passive skin anaphylaxis in rhesus monkeys is a model for studying IgG4-mediated allergic reactions.
• The Fc gamma receptor on mast cells plays a crucial role in allergic responses.

Purpose:

• To investigate the structural basis for functional differences in human IgG4 paraproteins.
• To correlate oligosaccharide structure with the ability to induce passive skin anaphylaxis.
• To determine if structural variations explain the differential binding of IgG4 paraproteins to Fc gamma receptors.

Summary:

• High-performance liquid chromatography (HPLC) analysis revealed distinct oligosaccharide structures in human IgG4 paraproteins.
• An atypical IgG4 paraprotein, non-reactive in passive skin anaphylaxis and non-binding to the IH2 monoclonal antibody, displayed a higher proportion of carbohydrate chains lacking terminal galactose residues compared to typical IgG4 paraproteins.
• This specific structural feature, the absence of terminal galactose, is proposed as a reason for the atypical IgG4's inability to bind the mast cell Fc gamma receptor.

Impact:

• Identifies a specific structural determinant (lack of terminal galactose) influencing IgG4 function.
• Provides insights into the molecular mechanisms underlying IgG4 subclass-specific interactions with Fc gamma receptors.
• Contributes to understanding the heterogeneity of IgG4-mediated immune responses and allergic reactions.