Identification of frequently recognized dimorphic T-cell epitopes in Plasmodium falciparum merozoite surface protein-1 in West and East Africans: Lack of correlation of immune recognition and allelic prevalence

The: merozoite surface protein-1 (MSP1) is the most studied malaria blood-s tage vaccine candidate. Lymphokines such as interferon gamma (IFN-gamma) an d interleukin 4 (IL-4) may mediate blood-stage specific protection Here we identify Plasmodium falciparum MSP1 T-cell epitopes capable of rapid induct ion of IFN-gamma and/or IL-4 from peripheral blood mononuclear cells of Eas t and West African donors. Both allelic forms of these novel MSP1 T-cell ep itopes were stimulatory. An unusually high numbers of Gambian responders (> 80%) to these epitopes were observed, suggesting that MSP1 reactivity may have been underestimated previously in this population. Surprisingly, IFN-g amma responses to allelic T-cell epitopes failed to correlate with differen tial antigenic exposure in The Gambia compared to Kenya. These results sugg est an unexpected level of immunoregulation of IFN-gamma response with vari able allelic T-cell reactivity independent of the level of antigenic exposu re. Further analysis of the mechanisms determining this response pattern ma y be required if vaccines are to overcome this allelic reactivity bias in m alaria-exposed populations.