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 clp heterodimer a nd that tolerance specifically induced to the H/K ATPase beta-subunit prote cts mice from the development of gastritis. Here we have identified the imm unodominant gastritogenic epitope of the H/K ATPase beta-subunit (H/K beta) . Epitope mapping was carried out with a panel of 21 overlapping peptides t hat spanned the entire sequence of the gastric H/K ATPase beta-subunit. T c ells from gastric H/K ATPase-immunized mice responded to only one of the ov erlapping peptides, namely H/K beta(253-277). Furthermore, a single subcuta neous immunization of 6-week-old BALB/c mice with the ATPase beta-subunit p eptides resulted in a T-cell response to only H/K beta(253-277). Multiple i mmunization with the overlapping H/K ATPase peptides demonstrated that H/K beta(253-277) was capable of inducing a mononuclear infiltrate specifically within the gastric mucosa. We conclude that H/K beta(253-277) is the domin ant gastritogenic epitope of the gastric H/K ATPase.