T-CELL EPITOPES RECOGNIZED WITHIN THE 65,000 MW HSP IN PATIENTS WITH IGA NEPHROPATHY

IgA nephropathy (IgAN) is the commonest cause of glomerulonephritis an d 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 wi th progressive IgAN. We examined the hypothesis that specific peptides within the 65 000 MW heat-shock protein (hsp) might stimulate TCR gam ma delta cells and play a part in the immunopathogenesis of IgAN. We s tudied T-cell proliferative responses stimulated by overlapping peptid es derived from the sequence of mycobacterial 65 000 MW hsp. Three T-c ell epitopes have been identified (peptides 51-65, 71-85 and 281-295). The three peptides have a synergistic effect and they stimulate signi ficantly higher proliferation of T cells in patients with IgAN than in disease or healthy controls. This response was inhibited by monoclona l 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 g amma delta(+) cells was confirmed by up-regulation of the proportion o f TCR gamma delta(+) cells when stimulated with the three specific pep tides. We suggest that IgAN might be associated with mucosal infection by a variety of micro-organisms and that peptides within the microbia l hsp cross-react with the homologous human hsp which may stimulate TC R gamma delta(+) cells and play a part in the pathogenesis of IgAN.