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T‐cell epitopes recognized within the 65 000 MW hsp in patients‘qc with IgA nephropathy
Author(s) -
WARR K.,
FORTUNE F.,
NAMIE‡ S.,
WILSON A.,
SHINNICK§ T.,
VAN DER ZEE¶ R.,
WILLIAMS G.,
LEHNER T.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00279.x
Subject(s) - epitope , nephropathy , immunology , chemistry , medicine , antibody , endocrinology , diabetes mellitus
IgA nephropathy (IgAN) is the commonest cause of glomerulonephritis and clinical exacerbation of IgAN is frequently associated with mucosal infection. T‐cell receptor γδ (TCR γδ + ) 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 γδ 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 γδ + and human leucocyte antigen (HLA) class I, but not by mAb to HLA class II. The involvement of TCR γδ + cells was confirmed by up‐regulation of the proportion of TCR γδ + 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 γδ + cells and play a part in the pathogenesis of IgAN.