title: Characterization of H+,K+-ATPase T cell epitopes in human autoimmune gastritis.
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, and the 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 Vbeta 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 a and beta chains of H+,K(+)-ATPase. We identified 6 epitopes in the a chain and 5 in the beta chain; TCR Vbeta 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 cytokine secretion and likely also with regard to pathogenic mechanisms.
authors.affiliation: Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mathijs P
authors.initials: MP
authors.lastname: Bergman
authors.forename: Amedeo
authors.initials: A
authors.lastname: Amedei
authors.forename: Mario M
authors.initials: MM
authors.lastname: D'Elios
authors.forename: Annalisa
authors.initials: A
authors.lastname: Azzurri
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.forename: Carlo
authors.initials: C
authors.lastname: Tamburini
authors.forename: Ruurd
authors.initials: R
authors.lastname: van der Zee
authors.forename: Christina M
authors.initials: CM
authors.lastname: Vandenbroucke-Grauls
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Appelmelk
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Del Prete
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D016384:Consensus Sequence; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000276:immunology; D005756:Gastritis / Q000201:enzymology / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000939:Epitopes; D010446:Peptide Fragments; D015847:Interleukin-4; D007371:Interferon-gamma; D006180:Proton-Translocating ATPases