Involvement of Pf155/RESA and cross-reactive antigens in Plasmodium falciparum merozoite invasion in vitro

Lines of Plasmodium falciparum FCR3 either expressing or not expressing the blood-stage antigen Pf155/RESA were used to analyze the possible involvement of this antigen in the merozoite invasion process in vitro. Antibodies from human sera, affinity purified on synthetic peptides corresponding to C-terminal repeated sequences in Pf155/RESA, were shown to inhibit merozoite invasion of both types of parasites with similar efficiency. Reversal of the invasion inhibition by fusion proteins containing repeated sequences of Pf155/RESA but not of the cross-reactive antigens Ag332 and Pf11.1 indicated that the inhibitory antibodies had similar target antigens in both Pf155/RESA+ and Pf155/RESA- parasites that involved cross-reacting epitopes present in Pf155/RESA. Rabbit antibodies specific for Pf155/RESA repeats inhibited merozoite invasion of Pf155/RESA expressing parasites efficiently but had no or very small effect on the invasion of Pf155/RESA-deficient parasites. In contrast, rabbit antibodies specific for Ag332 repeats as well as human antibodies affinity purified on synthetic Ag332 peptides inhibited merozoite invasion of both types of parasites with high efficiency. A similar inhibition pattern was seen with the human monoclonal antibody 33G2, which has specificity for Ag332 but also cross-reacts with Pf155/RESA and Pf11.1. Taken together, our data suggest that Pf155/RESA and related cross-reactive antigens as well as Ag332 are involved in the merozoite invasion process and may constitute targets for invasion inhibitory antibodies.

[1]  R. Udomsangpetch,et al.  Plasmodium falciparum: analysis of the interaction of antigen Pf155/RESA with the erythrocyte membrane. , 1991, Experimental parasitology.

[2]  M. Foley,et al.  The ring-infected erythrocyte surface antigen of Plasmodium falciparum associates with spectrin in the erythrocyte membrane. , 1991, Molecular and biochemical parasitology.

[3]  P. Perlmann,et al.  Definition of the epitope recognized by the Plasmodium falciparum-reactive human monoclonal antibody 33G2. , 1991, Molecular and biochemical parasitology.

[4]  R. Anders,et al.  Plasmodium falciparum ring-infected erythrocyte surface antigen is released from merozoite dense granules after erythrocyte invasion , 1991, Infection and immunity.

[5]  M. Aikawa,et al.  Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane. , 1991, Molecular and biochemical parasitology.

[6]  A. Sjölander,et al.  Pf155/RESA antigen is localized in dense granules of Plasmodium falciparum merozoites. , 1990, Experimental parasitology.

[7]  J. Ravetch,et al.  A and T homopolymeric stretches mediate a DNA inversion in Plasmodium falciparum which results in loss of gene expression , 1990, Molecular and cellular biology.

[8]  M. Uhlén,et al.  A general strategy for polymerization, assembly and expression of epitope-carrying peptides applied to the Plasmodium falciparum antigen Pf155/RESA. , 1990, Gene.

[9]  S. Viriyakosol,et al.  Cross-reactive asparagine-rich determinants shared between several blood-stage antigens of Plasmodium falciparum and the circumsporozoite protein. , 1990, Molecular and biochemical parasitology.

[10]  M. Uhlén,et al.  Immunogenicity and antigenicity in rabbits of a repeated sequence of Plasmodium falciparum antigen Pf155/RESA fused to two immunoglobulin G-binding domains of staphylococcal protein A , 1990, Infection and immunity.

[11]  M. Uhlén,et al.  A dual expression system for the generation, analysis and purification of antibodies to a repeated sequence of the Plasmodium falciparum antigen Pf155/RESA. , 1989, Journal of immunological methods.

[12]  J. Adams,et al.  Release of merozoite dense granules during erythrocyte invasion by Plasmodium knowlesi , 1989, Infection and immunity.

[13]  A. Cowman,et al.  Expression of the RESA gene in Plasmodium falciparum isolate FCR3 is prevented by a subtelomeric deletion , 1989, Molecular and cellular biology.

[14]  R. Udomsangpetch,et al.  Reactivity of the human monoclonal antibody 33G2 with repeated sequences of three distinct Plasmodium falciparum antigens. , 1989, Journal of immunology.

[15]  M. Wahlgren,et al.  Cross–reactive antigenic determinants present on different Plasmodium falciparum blood–stage antigens , 1989, Parasite immunology.

[16]  R. Coppel,et al.  MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton. , 1988, Molecular and biochemical parasitology.

[17]  R. Coppel,et al.  Antigens with repeated amino acid sequences from the asexual blood stages of Plasmodium falciparum. , 1988, Progress in allergy.

[18]  M. Wahlgren,et al.  Monoclonal antibodies to a synthetic peptide corresponding to a repeated sequence in the Plasmodium falciparum antigen Pf155. , 1988, Molecular and biochemical parasitology.

[19]  H. Shio,et al.  Secretion of Plasmodium falciparum rhoptry protein into the plasma membrane of host erythrocytes , 1988, The Journal of cell biology.

[20]  B. Müller-Hill,et al.  The 11‐1 gene of Plasmodium falciparum codes for distinct fast evolving repeats. , 1988, The EMBO journal.

[21]  M. Wahlgren,et al.  Absence of antigenic diversity in Pf155, a major parasite antigen in membranes of erythrocytes infected with Plasmodium falciparum , 1987, Journal of clinical microbiology.

[22]  R. Anders,et al.  Multiple cross‐reactivities amongst antigens of Plasmodium falciparum impair the development of protective immunity against malaria , 1986, Parasite immunology.

[23]  M. Wahlgren,et al.  Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Wahlgren,et al.  Human monoclonal antibodies to Pf 155, a major antigen of malaria parasite Plasmodium falciparum. , 1986, Science.

[25]  R. Houghten General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Wahlgren,et al.  Human antibodies to a Mr 155,000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Wahlgren,et al.  Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum , 1984, The Journal of experimental medicine.

[28]  N. Harboe,et al.  23. Immunization, Isolation of Immunoglobulins, Estimation of Antibody Titre , 1973, Scandinavian journal of immunology. Supplement.

[29]  T. Hadley Invasion of erythrocytes by malaria parasites: a cellular and molecular overview. , 1986, Annual review of microbiology.

[30]  A. Cowman,et al.  Immune sera recognize on erythrocytes a Plasmodium falciparum antigen composed of repeated amino acid sequences , 1984, Nature.

[31]  M S Doscher,et al.  Solid-phase peptide synthesis. , 1977, Methods in enzymology.