The 60- to 90-kDa parietal cell autoantigen associated with autoimmune gastritis is a beta subunit of the gastric H+/K(+)-ATPase (proton pump).
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.
Toh
B H
BH
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
Gleeson
P A
PA
Simpson
R J
RJ
Moritz
R L
RL
Callaghan
J M
JM
Goldkorn
I
I
Jones
C M
CM
Martinelli
T M
TM
Mu
F T
FT
Humphris
D C
DC
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
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