Immunopathogenesis of chronic human Chagasic cardiopathy: multi-disciplinary study of the biological relevance of cardiac myosin antigenic mimetism

• Grant number: 96/01440-7
• Support Opportunities: Research Projects - Thematic Grants
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Jorge Elias Kalil Filho
• Grantee: Jorge Elias Kalil Filho
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant(s): 99/00365-0 - A human post-infectoius autoimmune disease model, AR.EXT; 98/11427-3 - 1) autoimmunity in Human Chagas disease cardiomyopathy: t cell molecular mimicry and effector mechanisms, AR.EXT

Abstract

Although there is an accumulation of data suggesting the involvement of autoimmunity in the pathogenesis of chronic Chagasic cardiopathy, little attention has been directed at the identification of target-antigens in the cardiac tissue on in T.cruzi. Myosin, the most common protein in the heart is recognized by mice chronically infected by T. cruzi. Recently, we identified an epitope of human cardiac myosin (AAALDK) which is the target of molecular mimetism, revealed by antibodies, by the recombinant protein of T.cruzi B13 (AAAGDK). Furthermore, this epitope of crossed reaction is preferentially recognized by Chagasic cardiopaths, and not indeterminate. It was demonstrated also that clones of intracardiac T cells of Chagasic cardiopaths simultaneously recognize both proteins. In the present project, we propose a multi-disciplinary approach aimed at the study of several questions related to the biological role of B13 cardiac myosin antigenic mimetism and the mechanisms responsible for lesion in the cardiac tissue. These questions include: the structural characterization of the antigenic surface of the epitopes of crossed reaction B13-cardiac myosin in level of antibodies and T lymphocytes; the response of the activation of intralesional T lymphocytes to relevant antigens; the profile of production of lymphocines of clones of antigen-specific intralesional T lymphocytes or of peripheral blood of Chagasic patients; the evaluation of the cytotoxic activity of these last lymphocytes. (AU)