title: Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1.
abstract: 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.
authors.affiliation: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
authors.forename: Y P
authors.initials: YP
authors.lastname: Shi
authors.forename: U
authors.initials: U
authors.lastname: Sayed
authors.forename: S H
authors.initials: SH
authors.lastname: Qari
authors.forename: J M
authors.initials: JM
authors.lastname: Roberts
authors.forename: V
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: A J
authors.initials: AJ
authors.lastname: Oloo
authors.forename: W A
authors.initials: WA
authors.lastname: Hawley
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: B L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D007630:Kenya; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000737:chemistry / Q000494:pharmacology; D020066:Merozoite Surface Protein 1; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic