Changing ABRA protein peptide to fit into the HLA-DRbeta1*0301 molecule renders it protection-inducing.
The Plasmodium falciparum acidic-basic repeat antigen represents a potential malarial vaccine candidate. One of this protein's high activity binding peptides, named 2150 ((161)KMNMLKENVDYIQKNQNLFK(180)), is conserved, non-immunogenic, and non-protection-inducing. Analogue peptides whose critical binding residues (in bold) were replaced by amino-acids having similar mass but different charge were synthesized and tested to try to modify such immunological properties. These analogues' HLA-DRbeta1* molecule binding ability were also studied in an attempt to explain their biological mechanisms and correlate binding capacity and immunological function with their three-dimensional structure determined by (1)H NMR. A 3(10) distorted helical structure was identified in protective and immunogenic peptide 24922 whilst alpha-helical structure was found for non-immunogenic, non-protective peptides having differences in alpha-helical position. The changes performed on immunogenic, protection-inducing peptide 24922 allowed it to bind specifically to the HLA-DRbeta1*0301 molecule, suggesting that these changes may lead to better interaction with the MHC Class II-peptide-TCR complex rendering it immunogenic and protective, thus suggesting a new way of developing multi-component, sub-unit-based anti-malarial vaccines.
Salazar
Luz M
LM
Fundación Instituto de Inmunologia de Colombia (FIDIC), Cra 50 No. 26-00, Bogota, Colombia.
Alba
Martha P
MP
Curtidor
Hernando
H
Bermúdez
Adriana
A
Luis E  Vargas
Rivera
Zuly J
ZJ
Patarroyo
Manuel E
ME
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D000882:Haplorhini; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000953:Antigens, Protozoan; D006684:HLA-DR Antigens; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; C079596:p101-ABRA protein, Plasmodium falciparum