T cells recognize an immunodominant epitope of heat shock protein 65 in Kawasaki disease.
BACKGROUND
Kawasaki disease (KD) is an acute systemic vasculitis of infancy and early childhood that is characterized by endothelial cell damage associated with T-cell activation. Lymphocytes infiltrating damaged tissues might be responsible for the disease through secretion of cytokines, such as tumor necrosis factor (TNF)-alpha, that could cause fever, as well as endothelial tissue damage. Debate is growing about the nature of antigen responsible for T-cell activation in KD. Bacillus Calmette Guerin (BCG) and purified 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.


METHODS
CD4+ and CD8+ T-cell clones were obtained from peripheral blood of KD patients in acute phase, or control subjects. The clones were tested for reactivity toward HSP65 and derived peptides. Both proliferation and cytokine production were analyzed.


RESULTS
A significant fraction of CD4 and CD8 T-cell clones from KD patients recognized an epitope from 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 and human HSP could play a role in the development of the tissue-damage characteristic of KD.
Sireci
G
G
Department of Biopathology, University of Palermo, Italy.
Dieli
F
F
Salerno
A
A
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002555:Cerebrospinal Fluid / Q000166:cytology; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009080:Mucocutaneous Lymph Node Syndrome / Q000209:etiology / Q000276:immunology*; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014373:Tuberculin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D011994:Recombinant Proteins; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins