Lectin-carbohydrate interactions in disease. T-cell recognition of IgA and IgD; mannose binding protein recognition of IgG0.
Two disease associated lectin-carbohydrate interactions have been studied. (1) A T-cell surface lectin which binds IgA1 and IgD is expressed on CD4+ and CD8+ T-lymphocytes in a number of diseases including systemic lupus erythematosus, rheumatoid arthritis (RA), Behcet's disease and IgA nephropathy. We have demonstrated that calcium independent binding to this receptor is mediated by the O-linked disaccharide Gal beta 3GalNAc which is associated with the hinge regions of both IgA1 and IgD. (2) In rheumatoid arthritis the proportion of IgG0 glycoform populations lacking terminal galactose increases. We have shown that terminal GlcNAc residues on oligosaccharides in the Fc region of IgG0 can bind to the C-type lectin, serum mannose binding protein, and thus activate the classical complement pathway. This provides a mechanism of activation of the complement system not available to the other classes of IgG glycoforms.
Rudd
P
P
Department of Biochemistry, University of Oxford, United Kingdom.
Fortune
F
F
Lehner
T
T
Parekh
R
R
Patel
T
T
Wormald
M
M
Malhotra
R
R
Sim
R
R
Dwek
R
R
D050260:Carbohydrate Metabolism; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D003167:Complement Activation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007072:Immunoglobulin D / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism*; D037241:Mannose-Binding Lectins; D013601:T-Lymphocytes / Q000378:metabolism*
D002352:Carrier Proteins; D007070:Immunoglobulin A; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D037102:Lectins; D037241:Mannose-Binding Lectins