Modifying RESA protein peptide 6671 to fit into HLA-DRbeta1* pockets induces protection against malaria.
6671 is a non-immunogenic, conserved high activity red blood cell binding peptide located between residues 141 and 160 of the Plasmodium falciparum RESA protein. This peptide's critical red blood cell (RBC) binding residues have been replaced by amino acids having similar mass but different charge to change their immunologic properties. Three analogues (two of them immunogenic and protective and one immunogenic) were studied by purified HLA-DRbeta1* binding and NMR to correlate their structure with their immunological properties. Native peptide 6671 had a very flexible beta-sheet structure, whilst its immunogenic, protective, and non-protective peptide analogues presented an alpha-helical structure having different locations and lengths. These changes in peptide structure facilitated their fitting into HLA-DRbeta1* molecules. This paper shows for the first time how modifications performed on RESA protein non-immunogenic, non-protectogenic peptides impose a configuration allowing them to fit perfectly into the MHC II-TCR complex, in turn leading to appropriate activation of the immune system.
Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-00, Bogotá, Colombia.
Martha Patricia
MP
Alba
Luz Mary
LM
Salazar
Luis Eduardo
LE
Vargas
Mary
M
Trujillo
Yolanda
Y
Lopez
Manuel Elkin
ME
Patarroyo
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001665:Binding Sites; D002942:Circular Dichroism; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D000882:Haplorhini; D016778:Malaria, Falciparum / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D000953:Antigens, Protozoan; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010455:Peptides; D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum