The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H⁺/K⁺-ATPase (proton pump)

Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the α subunit of the gastric H⁺/K⁺-ATPase, an abundant gastric microsomal glycoprotein of apparent M(r) 60,000-90,000. Herein we have colocalized the glycoprotein and the α subunit of the gastric H⁺/K⁺-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the α subunit were coimmunoprecipitated, and copurified by immunoaffinity chromatography, with an anti-glycoprotein monoclonal antibody. The pig glycoprotein was purified by chromatography on tomato lectin-Sepharose, and five tryptic peptides from the purified glycoprotein were partially sequenced. The complete amino acid sequence, deduced from the nucleotide sequence of overlapping cDNA clones, showed 33% similarity to the sequence of the β subunit of the pig kidney Na⁺/K⁺-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the β subunit of the gastric H⁺/K⁺-ATPase and that the α and β subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.