title: Identification of T and B cell epitopes recognized by humans in the C-terminal 42-kDa domain of the Plasmodium falciparum merozoite surface protein (MSP)-1.
abstract: The 42-kDa, C-terminal region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a putative malaria vaccine candidate Ag. Nine synthetic peptides corresponding to predicted T cell sites of MSP-1 in blocks 15 and 16 and eight overlapping peptides representing the conserved block 17 were used to identify naturally immunogenic epitopes. These peptides were tested for their ability to induce proliferation of PBMC from residents in western Kenya, where malaria transmission is holoendemic. Six peptides (PL145, PL146, PL147, PL148, PL149, and PL150) from blocks 15 and 16 induced a positive proliferative response in > 30% of the individuals tested, and three peptides (PL151, PL152, and PL153) induced a proliferative response in < 25% of the donors. Among these peptides, PL146 was from the highly conserved region, PL150 was from a polymorphic region, and all other peptides were from a dimorphic region of blocks 15 and 16. In block 17, only three peptides, PL99, PL100, and PL103, induced proliferation in 30 to 37% of the volunteers. The rest of the peptides induced a proliferative response in approximately 13 to 25% of the donors. The plasma from these donors widely reacted with different allelic forms of 19-kDa recombinant proteins representing block 17 and recognized at least two linear B epitopes, PL104 and PL97. In summary, this study revealed that a majority of immunodominant T and B epitopes are localized in the conserved or dimorphic regions that are nonpolymorphic in the 42-kDa protein of MSP-1. This study suggests that incorporation of T epitopes from the dimorphic blocks 15 and 16 in a vaccine construct may be useful to ensure Ag-specific memory responses.
authors.affiliation: Immunology Branch, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
authors.forename: V
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: D
authors.initials: D
authors.lastname: Anyona
authors.forename: S
authors.initials: S
authors.lastname: Kariuki
authors.forename: Y P
authors.initials: YP
authors.lastname: Shi
authors.forename: P B
authors.initials: PB
authors.lastname: Bloland
authors.forename: O H
authors.initials: OH
authors.lastname: Branch
authors.forename: W
authors.initials: W
authors.lastname: Weiss
authors.forename: B L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins