Primary structure of the variable region of monoclonal antibody 2B10, capable of inducing anti-idiotypic antibodies that recognize the C-terminal region of MSA-1 of Plasmodium falciparum

Abstract

Previously, we reported on the properties of a monoclonal antibody, 2B10, which has the same determinant on the human erythrocyte as MSA-1 of Plasmodium falciparum (FCR3 strain); the binding of both ligands to erythrocyte receptors was totally sialic acid dependent. In this work, rabbit anti-2B10 idiotypic antibodies were generated. The anti-idiotypic antibodies recognized both the erythrocyte binding site of 2B10 and the Cterminal region of MSA-1 (amino acids 1047 to 1640); they were able to inhibit 2B10 and MSA-1 binding to erythrocytes and partially prevent P. falciparum merozoites from invading erythrocytes. The utility of 2B10 in the study of the interaction between MSA-1 and human erythrocytes prompted us to determine the nucleotide and deduced amino acid sequences of its V H and V L regions. The data show that the 2B10 V H region is part of the J558 family and is especially homologous to BALB/c anti-nitrophenyl monoclonal antibody 21.1.43; the V L region belongs to the VK1 subgroup and comes from the same genomic locus as (NZB ؋ W)F 1 anti-DNA and C57BL anti-dextran monoclonal antibodies BXW-14 and 42.48.12.2, respectively. Most of the differences among the V H and V L segments are located in CDR1 and-3. The binding site of 2B10 contains both negatively and positively charged amino acid residues. The amino acid sequences of the 2B10 V H region and a region of MSA-1 from the Wellcome strain of P. falciparum (amino acids 1002 to 1115) share 43% similarity, and the amino acid sequences between the 2B10 V L region and another segment of the same MSA-1 (amino acids 1247 to 1394) share 48% similarity. We conclude that the interactions between erythrocyte receptors and their ligands, 2B10 and MSA-1, are related and that the C-terminal region of MSA-1 is the erythrocyte binding domain.