T cells recognize an immunodominant epitope of heat shock protein 65 in Kawasaki disease

Background: Kawasaki disease (KD) is an acute systemic vasculitis of infanc y and early childhood that is characterized by endothelial cell damage asso ciated with T-cell activation. Lymphocytes infiltrating damaged tissues mig ht be responsible for the disease through secretion of cytokines, such as t umor necrosis factor (TNF)-alpha, that could cause fever, as well as endoth elial tissue damage. Debate is growing about the nature of antigen responsi ble for T-cell activation in KD. Bacillus Calmette Guerin (BCG) and purifie d protein derivative (PPD) hyperresponsiveness was observed in KD patients and this phenomenon was hypothetically ascribed to cross-reactivity between mycobacterial Heat Shock Protein (HSP) 65 and human homologue HSP63. Materials and Methods: CD4(+) and CD8(+) T-cell clones were obtained from p eripheral blood of KD patients in acute phase, or control subjects. The clo nes were tested for reactivity toward HSP65 and derived peptides. Both prol iferation and cytokine production were analyzed. Results: A significant fra ction of CD4 and CD8 T-cell clones from RD patients recognized an epitope f rom HSP65, spanning amino acids 65-85. T-cell clones cross-reacted with the corresponding 90-110 peptide sequence of human HSP-63. Conclusions: Cross-reactivity between specific epitopes of mycobacterial an d human HSP could play a role in the development of the tissue-damage chara cteristic of KD.