Our results additionally demonstrated that binding to CR1 of C1q occurs entirely independently of the Sl and McC-encoded variations. For rosette-disruption assays we chose parasite clone R29, on the grounds that it is the best-characterized CR1-sensitive P. falciparum rosetting strain . In previous work, no differences were observed between strains in response to various agents such as the CR1 mAb J3B11 and recombinant CR1 15�C17 ; on this basis it was decided not to initiate extensive testing of other strains for rosette disruption. Although our experiments were not conducted on variant versions of the full-length ectodomain, this is unCYT387 likely to have eroded their relevance in respect of the assays performed in this study. Interactions between long-homologous repeat D and long-homologous repeats A or B, but not C, would require an unfeasibly contorted architecture for the CR1 molecule. It also seems unlikely that CCPs 26�C30 are a requirement for a putative interaction between longhomologous repeats D and C. On the other hand, our focus on soluble truncations as opposed to membrane-bound variants does leave open a number of untested possibilities. In particular, although we observed no differences in self-associative properties of CR1 15�C25, it is possible that a stalk-like long-homologous repeat D is important for mediating the clustering of CR1 molecules . The relevance of CR1 clustering to merozoite invasion or rosetting has not been investigated but it has been reported to be important for cell deformability, motility of cells in microvasculature and hence the immune clearance role of CR1. It is also possible that Sl and McC-encoded sequence variations affect a putative interaction, of unknown physiological significance, with mannan binding lectin . Moreover, CR1 is displayed on other cell-types than erythrocytes and may have other functions than those tested in this study. Finally, we used C4b from pooled plasma and therefore we did not take account of polymorphic variation in C4 that also exhibits a non-uniform distribuion across geographical regions of origin. African-derived populations are characterized by a slightly higher incidence of a MG132 larger size-variant of CR1 , and high copy numbers of CR1 on erythrocytes as well as increased frequency of the Sl2 and McCb alleles . The current study makes a correlation between the last of these sources of polymorphic variation and malaria seem less likely. Nor does the data support hypotheses based on differential abilities amongst these Knops blood group antigenic variants to protect erythrocytes against cytolytic complement attack. Our C3b- and C4b-binding data suggest that all the variants will be equally good at clearing immune complexes, although our studies of soluble fragments did not take into account the possible roles in this respect of CR1 clustering.