The role of protein glycosylation in allergy.
The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single beta-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted.
Altmann
Friedrich
F
Divison of Biochemistry, Department of Chemistry, University of Natural Resources and Applied Life Sciences, Vienna, Austria. friedrich.altmann@boku.ac.at
D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D006967:Hypersensitivity
D000485:Allergens; D002241:Carbohydrates; D006023:Glycoproteins