Changing ABRA protein peptide to fit into the HLA-DRbeta1*0301 molecule renders it protection-inducing Academic Article

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

publication date

  • 2004/9/10

edition

  • 322

keywords

  • Amino Acids
  • Antigens
  • Antimalarials
  • Malaria Vaccines
  • Molecules
  • Nuclear magnetic resonance
  • Peptides
  • Plasmodium falciparum
  • Proteins
  • alpha-Helical Protein Conformation

International Standard Serial Number (ISSN)

  • 0006-291X

number of pages

  • 7

start page

  • 119

end page

  • 125