Identification of a gastritogenic epitope of the H/K ATPase beta-subunit.
We have previously shown that autoimmune gastritis can be elicited in mice by immunization with the gastric parietal cell H/K ATPase alpha beta heterodimer and that tolerance specifically induced to the H/K ATPase beta-subunit protects mice from the development of gastritis. Here we have identified the immunodominant gastritogenic epitope of the H/K ATPase beta-subunit (H/Kbeta). Epitope mapping was carried out with a panel of 21 overlapping peptides that spanned the entire sequence of the gastric H/K ATPase beta-subunit. T cells from gastric H/K ATPase-immunized mice responded to only one of the overlapping peptides, namely H/Kbeta253-277. Furthermore, a single subcutaneous immunization of 6-week-old BALB/c mice with the ATPase beta-subunit peptides resulted in a T-cell response to only H/Kbeta253-277. Multiple immunization with the overlapping H/K ATPase peptides demonstrated that H/Kbeta253-277 was capable of inducing a mononuclear infiltrate specifically within the gastric mucosa. We conclude that H/Kbeta253-277 is the dominant gastritogenic epitope of the gastric H/K ATPase.
De Silva
H D
HD
Department of Pathology and Immunology, Monash University Medical School, Melbourne, Australia.
Gleeson
P A
PA
Toh
B H
BH
Van Driel
I R
IR
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis*; D005753:Gastric Mucosa / Q000201:enzymology / Q000276:immunology*; D005756:Gastritis / Q000201:enzymology / Q000276:immunology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000276:immunology*; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D007527:Isoenzymes; D017506:H(+)-K(+)-Exchanging ATPase