Discussion

The haptoglobin-haemoglobin receptor (HpHbR) of Trypanosoma brucei allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. This talk will present our findings about the structure of the receptor and its mechanism of action in mediating ligand binding. We will describe the adaptations that have allowed TbHpHbR to bind to large ligands in the context of the densely packed VSG coat. We will show the effect of a receptor polymorphism that influences the uptake of trypanolytic factors in human infective T. b. gambiense. Finally, we will reveal the remarkable molecular and cellular adaptations that have occurred during the development of this receptor as it has diverged from an epimastigote expressed haemoglobin receptor in ancestral trypanosomes to a haemoglobin-haptoglobin receptor in T. brucei. These stories illustrate how a receptor can operate in the context of the trypanosome surface and how one receptor has evolved different roles in different trypanosome species.