Molecular analysis of the association of HLA-B53 and resistance to severe malaria.
The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010963:Plasmodium falciparum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014612:Vaccines
D000953:Antigens, Protozoan; D000939:Epitopes; D006680:HLA Antigens; C078438:HLA-B53 antigen; D009838:Oligodeoxyribonucleotides; D014612:Vaccines; C067302:liver stage-specific antigen, Plasmodium