Glycobiology, Vol 9, 601-606, Copyright © 1999 by Oxford University Press
LA Stewart, IR van Driel, BH Toh and PA Gleeson
The gastric H/K ATPase beta-subunit, an abundant glycoprotein of the
secretory membranes of gastric parietal cells, is the major autoantigen
recognized by human parietal cell autoantibodies in gastric autoimmunity.
Our previous studies demonstrated that the human autoantibodies recognize
the H/K ATPase beta-subunit from a number of species and that glycosylation
of the beta-subunit with complex N- glycans is required for autoantibody
binding. The N-glycans of the beta- subunit contain polylactosamine chains.
The lactosamine chains of the rabbit beta-subunit are terminated with
alpha-linked galactosyl residues (alpha-galactosyl epitope) (Tyagarajan et
al., Biochemistry, 1996, 35, 3238-3246). Here we have investigated the
expression of alpha- galactosyl epitopes on the H/K ATPase beta-subunit
from a number of species. Using the alpha-galactosyl binding lectin,
BS1-IB4, and naturally occurring anti-alpha-galactosyl antibodies, we have
demonstrated that the rat H/K ATPase beta-subunit also contains terminal
alpha-galactosyl residues, but not the beta-subunit from pig, dog, and
mouse, indicating species-specific differences in the terminal saccharide
sequences of the beta-subunit. We also investigated the potential
contribution of the alpha-galactosyl epitopes to the binding by human sera.
The reactivity of human pernicious anemia serum with gastric parietal cells
could not be inhibited with saccharide inhibitors and, in addition, no
binding was observed with normal human sera. We conclude that the H/K
ATPase beta-subunit oligosaccharides from rabbit and rat are terminated
with alpha-galactosyl epitopes, and although the presence of this epitope
does not contribute to binding by human parietal cell autoantibodies at the
concentrations routinely used, it is recommended that neither rat or rabbit
stomachs be used for screening human sera.
ORIGINAL ARTICLES
Species-specific distribution of alpha-galactosyl epitopes on the gastric H/K ATPase beta-subunit: relevance to the binding of human anti- parietal cell autoantibodies
Department of Pathology and Immunology, Monash University Medical School, Melbourne, Victoria, Australia.
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