Immunological fine structure of the variable and constant regions of a polymorphic malarial surface antigen from Plasmodium falciparum.
The 51-kDa merozoite surface antigen MSA2 of Plasmodium falciparum shows considerable strain-dependent polymorphism. Although marked sequence variation occurs in the central region of the molecule, the N and C-terminal sequences are highly conserved. A number of monoclonal antibodies directed against MSA2 have been described which inhibit parasite growth in vitro, but these are all directed against variable regions. In an attempt to raise strain independent antibodies we have prepared peptide-diphtheria toxoid (DT) constructs from 36 N-terminal octapeptides spanning the constant region and extending into the variable region of the FCQ/27 PNG variant staggered by one amino acid at either end. Similarly, we prepared 26 C-terminal octapeptides spanning the C-terminal constant region as well as 10 octapeptides from the variable region of the Indochina I variant MSA2. Most of the peptides elicited antipeptide titres in excess of 1/10(4) when administered to mice as peptide-DT adducts emulsified with Freund's complete adjuvant. Only 3 of the 43 N- and C-terminal constant region peptides elicited antibodies which reacted appropriately on immunofluorescence (IFA) or immunoblotting analysis with the intact MSA2 of both strains studied (FCQ/27 and Indochina I), whereas 3 other peptides from the variable region elicited antibodies reactive with the parent MSA2 only. Peptide constructs eliciting antibodies recognising the intact protein corresponded to elements in the cognate sequence of high antigenicity as predicted by the Jameson and Wolf algorithm.
Jones
G L
GL
Queensland Institute of Medical Research, Herston, Australia.
Edmundson
H M
HM
Lord
R
R
Spencer
L
L
Mollard
R
R
Saul
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics; D005260:Female; D007114:Immunization; D007120:Immunochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D016052:Protozoan Vaccines / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D016052:Protozoan Vaccines