Infection of humans with the protozoan parasite Trypanosoma cruzi can lead to a debilitating chronic syndrome known as Chagas' disease. This disease, which is endemic in much of Central and South America, is characterized by progressive cardiomyopathy and neuropathy of the digestive tract. The pathogenetic basis of this disease remains elusive mainly because animal models capable of reproducing chronic pathology have not been available. Acute murine models have been useful in discerning certain aspects of host resistance, but the basic immunobiology of this infection remains poorly understood. Because T lymphocyte responses are critical to host resistance and may also play a role in Chagas' disease pathogenesis, it is proposed to study the nature and specificity of the murine anti-T. cruzi T cell response. Using T cell cloning and T cell hybridoma technology, a panel of Tc- specific T cell reagents are being generated from Tc-infected mice. These T cell clones/hybridomas are being characterized to determine their in vitro and in vivo function and antigen specificity. Recombinant DNA technology will be used to clone and express the parasite genes encoding these antigens and to localize the precise T cell antigenic determinants recognized. Finally, recombinant antigens or synthetic peptides will be tested in vivo for T cell immunogenicity.
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