Abstract
Human autoimmune gastritis (AIG) is an organ‐specific inflammatory disorder leading to gastric atrophy and pernicious anemia. Gastric H^+^,K^+^‐ATPase was identified as the autoantigen in both human disease and experimental murine AIG (EAIG). Studies of EAIG significantly contributed to current knowledge of human AIG, but to what extent EAIG mimics AIG is still debated, andthe autoantigenic epitopes in AIG are yet unknown. This study aimed to identify the H^+^,K^+^‐ATPase epitopes recognized by gastric T cell clones from AIG patients, to define their TCR Vβ usage and epitope‐induced cytokine response. Sixteen H^+^,K^+^‐ATPase‐reactive CD4^+^ gastric T cell clones of four AIG patients were tested for proliferation to overlapping 15‐mer peptides spanning the α and β chains of H^+^,K^+^‐ATPase. We identified 6 epitopes in the α chain and 5 in the β chain; TCR Vβ usage was not restricted. Four (36%) of the 11 H^+^,K^+^‐ATPase epitopes recognized in AIG were found to overlap with epitopes that are relevant in EAIG, including a previously described gastritogenic epitope. Gastric T cell recognition of the peptide epitopes resulted in secretion of Th1 cytokines. Our data suggest a striking similarity between human AIG and EAIG, at the epitope level, with regard to cytokinesecretion and likely also with regard to pathogenic mechanisms.