Two MSA 2 peptides that bind to human red blood cells are relevant to Plasmodium falciparum merozoite invasion.
Plasmodium falciparum merozoite membrane surface antigen 2 (MSA2) has been associated with the development of protective immunity against malaria. MSA2 antibodies were able to inhibit in vitro merozoite invasion. In our search for experimental evidence concerning the participation of MSA2 in merozoite invasion, 40 peptides were synthesized according to sequences reported for the CAMP and FC27 prototype Plasmodium strains. These peptides were purified, 125I-radiolabeled and tested for their ability to bind to erythrocytes. Two MSA2 synthetic peptides with high specific binding to human erythrocytes were found. The peptide coded 4044 (KNESKYSNTFINNAYNMSIR), located in the MSA2 N-terminal conserved region, has an affinity coefficient of 72 nM and showed a positive cooperativity for the receptor-ligand interaction. The other peptide, coded 4053 (NPNHKNAETNPKGKGEVQKP) and located in the central variable region of MSA2, has an affinity coefficient of 49nM and also showed a positive cooperativity for the receptor-ligand interaction. The binding capacity of these peptides is affected by erythrocytes treated with neuraminidase and trypsin, but it is not affected by chymotrypsin. Both of these sequences inhibit in vitro erythrocyte parasite invasion by up to 95% suggesting that they have an important role in the parasite's invasion process. Furthermore, as published previously [A. Saul et al. (1992) J. Immunol., 148, 208-211], a protective B epitope is included in the 4044 peptide sequence.
Ocampo
M
M
Instituto de Immunología, Hospital San Juan de Dios, Universidad Nacional de Colombia, Bogotá.
Urquiza
M
M
Guzmán
F
F
Rodriguez
L E
LE
Suarez
J
J
Curtidor
H
H
Rosas
J
J
Diaz
M
M
Patarroyo
M E
ME
D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology; D000954:Antigens, Surface / Q000737:chemistry; D001667:Binding, Competitive; D002918:Chymotrypsin / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D009439:Neuraminidase / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology; D014357:Trypsin / Q000378:metabolism
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; D009439:Neuraminidase; D002918:Chymotrypsin; D014357:Trypsin