We have characterized the natural immune responses to the 19-kDa domain of
merozoite surface protein 1 in individuals from an area of western Kenya in which
malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR
antigens. T-cell proliferative responses in individuals older than 15 years and the profile 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, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant
antigens was observed in different individuals, suggesting that the 19-kDa
antigen may contain variant-specific T
epitopes. Among responses of the different isotypes of the
IgG antibody,
IgG1 and
IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of
IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that
IgG1 antibody response may play a role in protection against
malaria. However, there was no correlation between the
IgG3 antibody level and protection. Furthermore, we observed that although the natural
antibodies cross-reacted with all three variant 19-kDa
antigens,
IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR
antigen. This result suggests that the fine specificity of
IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second
epidermal growth factor domain (KNG and TSR) of the
antigen.