Analysis of fine specificity on the individual constituents of peptide pool 11 showed the same pattern for all positive samples collected from this child with recognition of peptides # 46, 61 and 74, namely of the K1-specific block1-block2 junction (Figure 10B). The occurrence of clinical malaria episodes in this child resulted in temporarily reduced signals (hence antibody levels), but was not associated with stable acquisition of any novel specificity. Figure 10 Serological longitudinal follow up of child 01/13 from 6 months to 6 years RG-7388 of age. Antibodies were assayed on 16 pools of biotinylated peptides (A) and to each individual peptide from

positive pool 11 (B). The peptide sequence and composition of the pools are described in Table 5. The dates of blood sampling are shown to the right of the graph. A. reactivity on the peptide pool. B. reactivity of three representative blood samples on individual peptides from pool 11. Discussion This first detailed longitudinal survey of Pfmsp1 block2 sequence polymorphism along with the assessment of the specific humoral response within a single endemic setting provides novel insights on the locus at the population level and on the possible selective forces underpinning such a polymorphism. A very large local polymorphism Pifithrin �� was detected, mainly due to microsatellite type variation, resulting in a very large

number of low frequency alleles. Numerous novel alleles were identified here, including novel MR alleles, illustrating Clomifene the value of in depth analysis of local polymorphism. The humoral response of the villagers, as deduced from the reaction with a series of 15-mer peptides, displayed features that illuminate its possible role in selection for diversity. The relative distribution of the family-specific antibody responses mirrored the relative distribution of the family types at the parasite population level. Seroprevalence was moderate.

Responses were usually limited to a single family and frequently directed to family-specific sequences present in most of the alleles from that family circulating in the village. This is consistent with a frequency-dependent selection operating at the family level. However, the serological analysis did not outline frequent occurrence of immune responses possibly selecting for sequence variants within that family. It confirmed and expanded on previous observations in this setting [27] of an essentially fixed antibody specificity, despite intense exposure to a very large number of allelic types. Overall, the data point to a possibly antibody-driven diversifying selection maintaining balanced family types within the population, as proposed by other groups [3, 12, 23, 24, 28, 33] but do not support the commonly accepted notion that the families accumulate mutations that allow the parasite to circumvent the host’s capacity to build up an efficient immune response selecting for sequence variants.