Pigeon fanciers' lung: identification of disease-associated carbohydrate epitopes on pigeon intestinal mucin.
Pigeon intestinal mucin, a complex high molecular weight glycoprotein, is a key antigen in the development of pigeon fanciers' lung (PFL). We have studied the specificity of antibodies to mucin in patients with PFL and asymptomatic antibody-positive individuals. Extensive papain digestion, which removes the non-glycosylated regions of the mucin leaving the heavily glycosylated 'bottle brush' regions, resulted in a 600-fold decrease in IgG3 antibody titres with little effect on IgG1 and IgG2 titres. This suggests that IgG1 and IgG2 are directed against the region rich in O-linked sugar chains whilst the majority of the IgG3 is directed against epitopes which are proteinase-sensitive. Lectin mapping of the carbohydrates present on pigeon intestinal mucin demonstrated high levels of exposed N-acetyl neuraminic acid, N-acetyl galactosamine and N-acetyl glucosamine, with lower levels of fucose and some galactose. Sera from pigeon fanciers inhibited binding of lectins specific for N-acetyl neuraminic acid, N-acetyl galactosamine, internal N-acetyl glucosamine and fucose. Sera from people with PFL, compared with sera from asymptomatic antibody-positive fanciers, had significantly higher titres of antibody that inhibited binding of four lectins specific for N-acetyl galactosamine and one fucose-specific lectin, suggesting that these sugars may play a dominant role in disease-associated epitopes. The results suggest that different IgG subclasses recognize different epitopes on mucin and that the epitopes recognized by the major subclasses are present on the O-linked oligosaccharides. Further, the carbohydrate-specific anti-mucin antibodies produced by PFL patients may differ in their specificity from those found in asymptomatic individuals.
Baldwin
C I
CI
Department of Physiological Sciences, The Medical School, University of Newcastle upon Tyne, UK. c.i.baldwin@newcastle.ac.uk
Todd
A
A
Bourke
S J
SJ
Allen
A
A
Calvert
J E
JE
D000818:Animals; D000918:Antibody Specificity; D001667:Binding, Competitive / Q000276:immunology; D001716:Bird Fancier's Lung / Q000276:immunology*; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000276:immunology*; D010856:Columbidae / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D037102:Lectins / Q000378:metabolism; D008297:Male; D009077:Mucins / Q000276:immunology* / Q000378:metabolism; D010206:Papain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010449:Peptide Mapping; D011485:Protein Binding / Q000276:immunology
D002241:Carbohydrates; D000939:Epitopes; D007074:Immunoglobulin G; D037102:Lectins; D009077:Mucins; D010446:Peptide Fragments; D010206:Papain