title: T-cell epitopes recognized within the 65,000 MW hsp in patients with IgA nephropathy.
abstract: IgA nephropathy (IgAN) is the commonest cause of glomerulonephritis and clinical exacerbation of IgAN is frequently associated with mucosal infection. T-cell receptor gamma delta (TCR gamma delta+) cells are increased in both the circulation and in renal biopsies of patients with progressive IgAN. We examined the hypothesis that specific peptides within the 65,000 MW heat-shock protein (hsp) might stimulate TCR gamma delta cells and play a part in the immunopathogenesis of IgAN. We studied T-cell proliferative responses stimulated by overlapping peptides derived from the sequence of mycobacterial 65,000 MW hsp. Three T-cell epitopes have been identified (peptides 51-65, 71-85 and 281-295). The three peptides have a synergistic effect and they stimulate significantly higher proliferation of T cells in patients with IgAN than in disease or healthy controls. This response was inhibited by monoclonal antibodies (mAb) to TCR gamma delta+ and human leucocyte antigen (HLA) class I, but not by mAb to HLA class II. The involvement of TCR gamma delta+ cells was confirmed by up-regulation of the proportion of TCR gamma delta+ cells when stimulated with the three specific peptides. We suggest that IgAN might be associated with mucosal infection by a variety of micro-organisms and that peptides within the microbial hsp cross-react with the homologous human hsp which may stimulate TCR gamma delta+ cells and play a part in the pathogenesis of IgAN.
authors.affiliation: Department of Immunology, United Medical School of Guy's Hospital, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Warr
authors.forename: F
authors.initials: F
authors.lastname: Fortune
authors.forename: S
authors.initials: S
authors.lastname: Namie
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: T
authors.initials: T
authors.lastname: Shinnick
authors.forename: R
authors.initials: R
authors.lastname: Van der Zee
authors.forename: G
authors.initials: G
authors.lastname: Williams
authors.forename: T
authors.initials: T
authors.lastname: Lehner
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001426:Bacterial Proteins; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000939:Epitopes; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins