Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants.
We have previously identified a Plasmodium falciparum liver stage-specific Ag (LSA-1) found to encode tandem 17 amino acid repeats harboring B cell determinants. Here we extend this study in terms of sequence analysis, protein localization, and immunologic properties. Analysis of the N- and C-terminal regions of LSA-1 from the T9/96 clone reveals high sequence conservation with LSA-1 from NF54. This 200-kDa protein is detected throughout liver schizogony and accumulates in the parasitophorous vacuole space. In our investigation of T and B cell responses to LSA-1, we have focused on both the area of the C-terminal, nonrepetitive "hinge" region and the conserved repetitive region and derived synthetic peptides. These were found to contain major B and T cell determinants. High prevalences and elevated Ab levels to LSA-1, directed primarily, although not exclusively, to the repetitive region, were detected in sera of individuals from one moderately high and two low transmission malaria-endemic areas (prevalences of 97%, 75, and 77%, respectively). In one of these low transmission areas, secretion of the cytokine IFN-gamma, known to inhibit malaria liver stages, and T cell proliferation were detected in PBMC of 22 to 48% and 6 to 20%, respectively, of individuals in response to separate LSA-1 peptides. These results complement the recent finding of conserved CTL epitopes in LSA-1 and support the assertion that immune responses to LS Ag are involved in protection against malaria pre-erythrocytic stages.
Fidock
D A
DA
Bio-Medical Parasitology Laboratory, Pasteur Institute, Paris, France.
Gras-Masse
H
H
Lepers
J P
JP
Brahimi
K
K
Benmohamed
L
L
Mellouk
S
S
Guerin-Marchand
C
C
Londono
A
A
Raharimalala
L
L
Meis
J F
JF
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002942:Circular Dichroism; D000939:Epitopes; D017125:Genes, Protozoan; D006801:Humans; D008099:Liver / Q000469:parasitology; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D017433:Protein Structure, Secondary; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; C067302:liver stage-specific antigen, Plasmodium