Changing ABRA protein peptide to fit into the HLA-DRbeta1*0301 molecule renders it protection-inducing |
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Authors: | Salazar Luz M Alba Martha P Curtidor Hernando Bermúdez Adriana Luis E Vargas Rivera Zuly J Patarroyo Manuel E |
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Institution: | Fundación Instituto de Inmunologia de Colombia (FIDIC), Cra 50 No. 26-00, Bogota, Colombia. |
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Abstract: | 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. |
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Keywords: | ABRA protein Peptide analogues Vaccine candidate Malaria Conformation NMR |
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