NATURAL IMMUNE-RESPONSE TO THE C-TERMINAL 19-KILODALTON DOMAIN OF PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1

We have characterized the natural immune responses to the 19-kDa domai n of merozoite surface protein 1 in individuals from an area of wester n Kenya in which malaria is holoendemic. We used the three known natur al variant forms of the yeast-expressed recombinant 19-kDa fragment th at are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell pro liferative responses in individuals older than 15 years and the profil e of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35 % of the individuals responded to the E-KNG and E-TSR constructs, resp ectively. Considerable heterogeneity in the T-cell proliferative respo nses to these three variant antigens was observed in different individ uals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antib ody, IgG1 and IgG3 isotype responses were predominant, and the prevale nce and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasi te density among young age groups, suggesting that IgG1 antibody respo nse may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Further more, we observed that although the natural antibodies cross-reacted w ith all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma sa mples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antib odies differentiates among variant-specific natural B-cell determinant s in the second epidermal growth factor domain (KNG and TSR) of the an tigen.