Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein.
The immunogenicity of multiple antigen peptides (MAP) constructs containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite (CS) protein was examined in vitro, using a human T cell clone, and in vivo, using four different strains of mice. All the MAP constructs that contained the T cell epitope, (DPNANPNVDPNANPNV), stimulated proliferation and interferon-gamma production by a human T cell clone specific for this epitope which is located in the 5' end of the repeat region of the P. falciparum CS protein. These human T cells did not recognize MAP that contained only the B cell epitope, (NANP)3, which is located in the 3' repeat region. Optimal antibody responses were obtained in mice immunized with MAP containing four copies of tandemly arranged T and B cell epitopes, (TB)4. The murine immune response to the MAP constructs was genetically restricted. Mice of a high responder strain, C57BL, recognized both the 5' and 3' repeat sequences in the MAP as T, as well as B, cell epitopes and developed very high anti-MAP and anti-sporozoite antibody titers. A/J and C3H mice, which were intermediate responders, developed lower antibody titers which varied according to the orientation of the T vs. the B cell epitopes within the MAP constructs. BALB/c mice were nonresponders and did not develop antibodies following immunization with any of the MAP constructs containing the 5' and 3' repeats of the P. falciparum CS protein.
Munesinghe
D Y
DY
Department of Zoology, University of Colombo, Sri Lanka.
Clavijo
P
P
Calle
M C
MC
Nussenzweig
R S
RS
Nardin
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan