title: The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K(+)-ATPase (proton pump).
abstract: Autoantibodies in the sera of patients with pernicious anemia recognize, in addition to the alpha subunit of the gastric H+/(+)-ATPase, an abundant gastric microsomal glycoprotein of apparent Mr 60,000-90,000. Herein we have colocalized the glycoprotein and the alpha subunit of the gastric H+/K(+)-ATPase to the tubulovesicular membranes of the parietal cell by immunogold electron microscopy. Moreover, the glycoprotein and the alpha 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 beta subunit of the pig kidney Na+/K(+)-ATPase. We therefore propose that the 60- to 90-kDa glycoprotein autoantigen is the beta subunit of the gastric H+/K(+)-ATPase and that the alpha and beta subunits of the proton pump are major targets for autoimmunization in autoimmune gastritis.
authors.affiliation: Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
authors.forename: B H
authors.initials: BH
authors.lastname: Toh
authors.forename: P A
authors.initials: PA
authors.lastname: Gleeson
authors.forename: R J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: R L
authors.initials: RL
authors.lastname: Moritz
authors.forename: J M
authors.initials: JM
authors.lastname: Callaghan
authors.forename: I
authors.initials: I
authors.lastname: Goldkorn
authors.forename: C M
authors.initials: CM
authors.lastname: Jones
authors.forename: T M
authors.initials: TM
authors.lastname: Martinelli
authors.forename: F T
authors.initials: FT
authors.lastname: Mu
authors.forename: D C
authors.initials: DC
authors.lastname: Humphris
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification; D001324:Autoantigens / Q000235:genetics* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D001483:Base Sequence; D004285:Dogs; D005455:Fluorescent Antibody Technique; D005756:Gastritis / Q000201:enzymology / Q000276:immunology*; D017506:H(+)-K(+)-Exchanging ATPase; D006801:Humans; D046911:Macromolecular Substances; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010295:Parietal Cells, Gastric / Q000201:enzymology*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011061:Poly A; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase