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. MSA 2 antibodies were able to inhibit in vitro merozoite invasion. In our searc h for experimental evidence concerning the participation of MSA2 in merozoi te invasion, 40 peptides were synthesized according to sequences reported f or the CAMP and FC27 prototype Plasmodium strains. These peptides were puri fied, I-125-radio labeled and tested for their ability to bind to erythrocy tes. Two MSA2 synthetic peptides with high specific binding to human etythr ocytes were found. The peptide coded 4044 (KNESKYSNTFINNAYNMSIR), located i n the MSA2 N-terminal conserved region, has an affinity coefficient of: 72n M and showed a positive cooperativity for the receptor-ligand interaction. The other peptide, coded 4053 (NPNHKNAETNPKGKGEVQKP) and located in the cen tral variable region of MSA2 has an affinity coefficient of 49nM and also s howed a positive cooperativity for the receptor-ligand interaction. The bin ding capacity of these peptides is affected by erythrocytes treated with ne uraminidase and trypsin, but it is not affected by chymotrypsin. Both of th ese sequences inhibit in vitro erythrocyte parasite invasion by up to 95% s uggesting that they have an important role in the parasite's invasion proce ss. Furthermore, as published previously [A. Saul ef al. (1992) J. Immunol. , 148, 208-211], a protective B epitope is included in the 4044 peptide seq uence.