Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis.

Objective: To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA).

Methods: We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan-HLA-DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells.

Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein-Barr virus proteins in oligoarticular juvenile idiopathic arthritis.

Objective: To evaluate whether abnormal T cell recognition may be generated by exposure to exogenous antigens presenting sequence homology with epitopes contained in self HLA alleles, and if such recognition may be part of the mechanisms that fuel inflammation in autoimmune diseases associated with certain HLA alleles.

Methods: Cytotoxic responses of peripheral blood mononuclear cells to 9-mer peptides derived from HLA molecules (DRB1*1101, DRB1*0801, or DPB1*0201) associated with oligoarticular juvenile idiopathic arthritis (JIA) or homologous peptides derived from Epstein-Barr virus (EBV) proteins (Bolf1 or Balf2) were analyzed in patients with oligoarticular JIA and in healthy controls matched for HLA-DRB1*1101, DRB1*0801, or DPB1*0201. Production of proinflammatory cytokines in culture supernatants was determined by enzyme-linked immunosorbent assay.