Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting

Malaria Infection Induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen Is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens In malaria Immune subjects is due to HLAmedlated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozolte surface antigens (MSP1 and MSP2) and a sexual stage antigen (Pfs260/230) of Plasmodium falclparum, and conclude that host genotype is not a major determinant of responsivenes s. Although antibody levels vary in . accordance with seasonal variations In malaria transmission In semi-immune children, antibody levels remain stable In clinically immune adults. Antigen recognition Is selective with Individual donors showing consistent high tttre responses to some antigens/epitopes whilst consistently falling to recognize adjacent reglons/epltopes from the same protein. An alternative explanation, consistent with the data presented here, Is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal Imprinting (original antigenlc sin).