Identification of a gastritogenic epitope of the H/K ATPase β‐subunit

SUMMARY We have previously shown that autoimmune gastritis can be elicited in mice by immunization with the gastric parietal cell H/K ATPase ab heterodimer and that tolerance specifically induced to the H/K ATPase b-subunit protects mice from the development of gastritis. Here we have identified the immunodominant gastritogenic epitope of the H/K ATPase b-subunit (H/Kb). Epitope mapping was carried out with a panel of 21 overlapping peptides that spanned the entire sequence of the gastric H/K ATPase b-subunit. T cells from gastric H/K ATPase-immunized mice responded to only one of the overlapping peptides, namely H/Kb 253‐277 . Furthermore, a single subcutaneous immunization of 6-week-old BALB/c mice with the ATPase b-subunit peptides resulted in a T-cell response to only H/Kb 253‐277 . Multiple immunization with the overlapping H/K ATPase peptides demonstrated that H/Kb 253‐277 was capable of inducing a mononuclear infiltrate specifically within the gastric mucosa. We conclude that H/Kb 253‐277 is the dominant gastritogenic epitope of the gastric H/K ATPase.