CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein.
CD4+ T cell clones were derived from three volunteers who were protected against malaria after immunization with Plasmodium falciparum sporozoites. T cells specific for an epitope, Pf Th/Tc, contained in amino acids 326 to 345 of the circumsporozoite (CS) protein of P. falciparum (NF54) were derived from all three volunteers. DR1-, -4-, -7-, and -9-restricted T cell clones were found to recognize overlapping, but distinct, epitopes within a 20-mer peptide representing the amino acid 326 to 345 sequence. The Pf Th/Tc epitope contains part of the highly conserved region II as well as part of a polymorphic domain of the P. falciparum CS protein. All of the overlapping epitopes within peptide 326-345 contained at least three amino acids of the amino terminus of the conserved region II, in addition to a variable number of amino acids in the polymorphic region. The DR4-, -7-, and -9-restricted but not the DR1-restricted T cell clones recognized variant peptides representing this polymorphic region of the CS protein of P. falciparum isolates from Africa, Asia, and South America.
Moreno
A
A
Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010.
Clavijo
P
P
Edelman
R
R
Davis
J
J
Sztein
M
M
Sinigaglia
F
F
Nardin
E
E
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006681:HLA-D Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011110:Polymorphism, Genetic; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D008222:Lymphokines; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan