AUTOIMMUNITY IN CHAGAS-DISEASE - IDENTIFICATION OF CARDIAC MYOSIN-B13TRYPANOSOMA-CRUZI PROTEIN CROSS-REACTIVE T-CELL CLONES IN HEART LESIONS OF A CHRONIC CHAGAS CARDIOMYOPATHY PATIENT

Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CC C) may be caused by autoimmune recognition of heart tissue by a mononu clear cell infiltrate decades after Trypanosoma cruzi infection. Indir ect evidence suggests there is molecular mimicry between T. cruzi and heart tissue. In murine models of CCC, antibodies and CD4+ T cells rec ognize myosin, the major heart protein. We recently identified a heart -specific epitope of cardiac myosin heavy chain (residues 1442-1447, A AALDK) that is crossreactive with a homologous sequence (AAAGDK) of th e immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin-B13 crossreactive antibodies are present in 100% CCC patients vs 14% asym ptomatic T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggest ing a role for molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this paper, we obtained heart-infiltrating T cell cl ones from CCC patients to assess whether molecular mimicry between car diac myosin and B13 is directly involved in the genesis of heart lesio ns. We identified T cell clones derived from CCC heart lesions simulta neously responsive to cardiac myosin heavy chain (but not skeletal myo sin heavy chain) and B13 T. cruzi protein, but could not find T cell c lones primarily reactive to any T. cruzi antigen. Together with the as sociation of myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest the relevance of molecular mimicry between card iac myosin and the T. cruzi protein B13 in the pathogenesis of heart l esions in chronic Chagas' disease cardiomyopathy.