Orientating peptide residues and increasing the distance between pockets to enable fitting into MHC-TCR complex determine protection against malaria.
The erythrocyte binding antigen EBA-175 is a 175-kDa Plasmodium falciparum protein, which has been shown to be involved in the process of invasion of erythrocytes. It has been found that conserved peptide 1818 belonging to this protein has high red blood cell binding capacity and plays an important role in the invasion process. This peptide is neither immunogenic nor protective. Peptide 1818 analogues had some of their previously recognized critical red blood cell binding residues substituted for amino acids having similar volume or mass but different polarity to make them fit into HLA-DRbeta(1)*1101 molecules; these 1818 peptide analogues were then synthesized and inoculated into Aotus nancymaae monkeys, generating different immunogenic and/or protective immune responses. Short structures such as 3(10)-helix, classical, or distorted type-III beta-turns were found in the immunogenic and protective peptides once the secondary structure had been analyzed by NMR and its structure correlated with its immunological properties. These data suggest that peptide flexibility may lead to better fitting into immune system molecules, therefore making them excellent candidates for consideration as components of a subunit-based, multicomponent synthetic antimalarial vaccine.
Cifuentes
Gladys
G
Fundación Instituto de Inmunología de Colombia, Carrera 50 N. 26-00 Bogotá 020304 Colombia.
Espejo
Fabiola
F
Vargas
Luis Eduardo
LE
Parra
Carlos
C
Vanegas
Magnolia
M
Patarroyo
Manuel Elkin
ME
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D016645:Aotidae; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D006684:HLA-DR Antigens / Q000378:metabolism; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D000953:Antigens, Protozoan; D002352:Carrier Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell; D014614:Vaccines, Synthetic; C065668:erythrocyte-binding antigen 175, Plasmodium