African trypanosomes, unicellular parasites transmitted by the bite of a tsetse fly, thrive in the bloodstream of their mammalian host, evading the immune response by switching one surface coat protein for another. A prominent trypanosome feature is an invagination of the cell membrane called the flagellar pocket, which appears to be protected from the host's immune system and contains invariant receptors that provide the parasite with nutrients and other factors that are essential for cell growth. The few characterized receptors have features that are unique from the host equivalent and thus represent potential targets for therapeutic intervention. We currently investigate two receptor systems: One comprises an uptake system for low-density lipoprotein (LDL), while the other is involved in binding and internalizing trypanolytic factors.

The lethal action of human plasma on Trypanosoma brucei has been known since 1902. Two trypanosome lytic factors (TLFs) have been identified: 1) TLF1, which is a well characterized minor subclass of HDL, and 2) TLF2, which is a nonlipoprotein, high molecular weight particle. Internalization of TLF1 of TLF2 by the parasite is essential for subsequent lysis. Two trypanosome subspecies, T. brucei gambiense and T. brucei rhodesiense, are resistant to TLF-mediated lysis and therefore cause human sleeping sickness. We are using biochemical, cell biological, and expression cloning techniques to identify the receptors for TLF1 and TLF2 and to ascertain their role in resistance to trypanolysis.