Authors
O J Macleod1; P MacGregor1; L Peacock3; S Hester2; S Mohammed2; W Gibson3; M K Higgins2; M Carrington1; 1 Department of Biochemistry, University of Cambridge, Cambridge; 2 Department of Biochemistry, University of Oxford, Oxford; 3 School of Veterinary Science, University of Bristol, Bristol; School of Biological Sciences, University of Bristol, Bristol Discussion
Trypanosoma brucei interacts with its hosts through proteins expressed on the external face of the plasma membrane. For example, the transferrin receptor takes up host transferrin and the haptoglobin haemoglobin (HpHb) receptor takes up host HpHb, as well as primate-specific innate immunity factor TLF1. What other molecular interactions are there between the trypanosome surface and the host? A GPI-anchored surface receptor has been identified that binds host complement factor H (FH). FH is a large glycoprotein of 155 kDa that regulates the innate immune system by inhibiting the alternative complement pathway and preventing cell lysis. We have characterized the trypanosome FH receptor at a molecular level, localizing receptor-ligand interactions to the N-terminal portion of the receptor to two domains of FH. In cultured trypanosomes, we have shown that the receptor is expressed in bloodstream and procyclic forms (BSF and PCF). Interestingly, expression levels in the BSF are rapidly and reversibly titratable depending on the concentration of a serum component. The receptor has been localized to the cell surface, and takes up fluorescently labelled ligands into BSF and PCF cells. These observations are the first identification of a direct interaction between the complement system and T. brucei, represent a further mechanism of immune evasion in mammalian blood, and demonstrate novel findings about trypanosome receptor functioning. 
