Peptides inducing short-lived antibody responses against Plasmodium falciparum malaria have shorter structures and are read in a different MHC II functional register.
The search for a rational method of developing an antimalarial vaccine (malaria caused by Plasmodium falciparum) consists of blocking receptor-ligand interaction. Conserved peptides derived from proteins involved in invasion and having strong red blood cell binding ability have thus been identified; immunization studies using Aotus monkeys revealed that these peptides were neither immunogenic nor protection-inducing. Some of these peptides induced long-lasting and very high antibody titers and protection when their critical red blood cell binding residues were replaced to change their immunological properties. Others induced short-lived antibodies that were not associated with inducing protection. The three-dimensional structure of the short-lived antibody-inducing peptide was determined by (1)H NMR. Their HLA-DRbeta1* molecule binding ability was also determined to ascertain the relationship among three-dimensional structure, their ability to bind to major histocompatibility complex class II molecules (MHC II), and possible short-lived antibody production. These short-lived antibody-inducing peptides were 6.8 +/- 0.5 A shorter between those residues theoretically coming into contact with pocket 1 and pocket 9 of HLA-DRbeta1* molecules to which they bind than immunogenic and protection-inducing peptides. These more compact alpha-helical structures suggest that these short-lived antibody-inducing peptides could have a structure more similar to those of native peptides than immunogenic and protective ones. Such shortening was associated with a shift in HLA-DRbeta1* molecule binding and a consequent shift in functional register reading, mainly by alleles of the same haplotype when compared with immunogenic protection-inducing HABPs, suggesting an imperfect and different conformation of the MHC II peptide-TCR complex.
Patarroyo
Manuel E
ME
Universidad Nacional de Colombia, Bogotá, Columbia. mepatarr@mail.com
Alba
Martha P
MP
Vargas
Luis E
LE
Silva
Yolanda
Y
Rosas
Jaiver
J
Rodríguez
Raúl
R
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000097:blood; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D016645:Aotidae; D001667:Binding, Competitive / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000097:blood / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D049670:History, 17th Century; D006801:Humans; D007117:Immunization, Secondary; D007279:Injections, Subcutaneous; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D013997:Time Factors
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments