title: Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient.
abstract: Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests there is molecular mimicry between T. cruzi and heart tissue. In murine models of CCC, antibodies and CD4+ T cells recognize myosin, the major heart protein. We recently identified a heart-specific epitope of cardiac myosin heavy chain (residues 1442-1447, AAALDK) that is crossreactive with a homologous sequence (AAAGDK) of the immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin-B13 crossreactive antibodies are present in 100% CCC patients vs 14% asymptomatic T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggesting a role for molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this paper, we obtained heart-infiltrating T cell clones from CCC patients to assess whether molecular mimicry between cardiac myosin and B13 is directly involved in the genesis of heart lesions. We identified T cell clones derived from CCC heart lesions simultaneously responsive to cardiac myosin heavy chain (but not skeletal myosin heavy chain) and B13 T. cruzi protein, but could not find T cell clones primarily reactive to any T. cruzi antigen. Together with the association of myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest the relevance of molecular mimicry between cardiac myosin and the T. cruzi protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease cardiomyopathy.
authors.affiliation: Laboratory of Transplantation Immunology, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, Brazil. edecunha@spider.usp.br
authors.forename: E
authors.initials: E
authors.lastname: Cunha-Neto
authors.forename: V
authors.initials: V
authors.lastname: Coelho
authors.forename: L
authors.initials: L
authors.lastname: Guilherme
authors.forename: A
authors.initials: A
authors.lastname: Fiorelli
authors.forename: N
authors.initials: N
authors.lastname: Stolf
authors.forename: J
authors.initials: J
authors.lastname: Kalil
mesh_terms: D000328:Adult; D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D002908:Chronic Disease; D003429:Cross Reactions; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009206:Myocardium / Q000276:immunology*; D009218:Myosins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D015800:Protozoan Proteins; D009218:Myosins