The long-term objectives of this research proposal are to study the biology of T lymphocytes that are reactive with Histoplasma capsulatum. To facilitate these studies, murine T cell clones and T cell hybrids that recognize Histoplasma antigens have been generated. The in vivo immunoregulatory function of T cell clones will be examined as well as their trafficking patterns. The capacity of T cell clones to produce soluble mediators will be studied. In addition, the requirements for Histoplasma antigen presentation to T cell hybrids will be delineated, and the nature of Histoplasma antigen recognized by T cell hybrids will be analyzed. Attempts will be made to generate clonotypic antibodies to T cell clones and T cell hybrids. Both an antisera and a monoclonal antibody will be produced. Clonotypic antibodies will be tested for their capacity to modulate the in vitro responses of Histoplasma-specific T cells. In addition, studies will be conducted to determine if clonotypic antibodies can modify experimental histoplasmosis in mice or if it can vaccinate mice against Histoplasma infection. Finally, clonotypic antibodies will be employed to characterize partially the surface receptor on cloned T cells or T cell hybrids that recognizes Histoplasma capsulatum.
