Such repeated sampling from the same sub-group may have biased the analysis of population polymorphism, in particular as successive clinical malaria attacks experienced by a child are each caused by “”novel”" parasite genotypes [48]. To assess the consequence of sequence diversity on antigenicity, Tariquidar and in the search for evidence of antibody-driven diversifying selection, we opted here for the use of synthetic peptides encompassing

a large number of sequence variants, rather than using recombinant proteins expressing an entire MSP1 block2 domain, which exposes selleck chemicals llc multiple antigenic determinants. Whereas recombinant proteins allow to study family cross-reactivity, recognition at the single epitope level is best monitored using synthetic peptides. selleck compound Individual MSP1 epitopes are displayed by short peptidic sequences, which are recognised by monoclonal antibodies [15] and human sera [15, 26, 27]. Use of synthetic peptides may result in underrepresenting certain epitopes, including conformational epitopes, and hence in underestimating the overall seroprevalence to the locus. However, interestingly this assessment using synthetic peptides outlined a strikingly similar relative distribution of family genotypes and family-specific antibodies in Dielmo, consistent with observations in other settings monitoring immune responses using recombinant

proteins [3, 23, 25, 28, 29, 31–33, 36]. The humoral response of the Dielmo villagers suggested a family-specific selection pressure rather than an antibody-mediated selection for sequence variants. Seroprevalence increased with age,

but the number of peptides recognised was unrelated to age. Most individuals had antibodies to one family only, and within that family, polymorphic sites as well as common repeat motifs and the more conserved family-specific sequences were recognised. Importantly, antibody specificity remained essentially fixed over time. Confirming previous observations in this setting [27], the long term longitudinal follow up showed that cumulated exposure to an increasing number of Pfmsp1 block2 alleles was usually not associated with stable acquisition of antibody specificities to additional sequence variants. 17-DMAG (Alvespimycin) HCl Analysis of anti-MSP1 block2 responses during a transmission season showed that some individuals experiencing a high density clinical episode had their pre-existing responses boosted, while antibodies were transiently undetectable in other patients. In some cases, novel specificities were acquired only transiently, since they were rarely detected a few weeks after the episode and undetected in subsequent longitudinal samplings, where a steady state, essentially stable specificity profile was consistently observed.