title: HLA-A2 supertype-restricted cell-mediated immunity by peripheral blood mononuclear cells derived from Malian children with severe or uncomplicated Plasmodium falciparum malaria and healthy controls.
abstract: Understanding HLA-restricted adaptive host immunity to defined epitopes of malarial antigens may be required for the development of successful malaria vaccines. Fourteen epitopes of preerythrocytic malarial antigens known to mediate cytotoxic T-lymphocyte responses against target cells expressing HLA-A2-restricted epitopes were synthesized and pooled based on antigen: thrombospondin-related anonymous protein (TRAP), circumsporozoite protein (CSP), and export protein 1 (Exp-1) peptides. HLA-A2 supertype (*0201, *0202, *0205, *6802) peripheral blood mononuclear cells collected from 774 Malian children, aged 3 months to 14 years, with severe Plasmodium falciparum malaria matched to uncomplicated malaria or healthy controls were stimulated with the HLA-A2-restricted peptide pools. Significant gamma interferon production, determined by enzyme-linked immunospot assay to at least one of the three peptide pools, was observed in 24/58 (41%) of the severe malaria cases, 24/57 (42%) of the uncomplicated malaria cases, and 34/51 (67%) of the healthy controls. Significant lymphoproliferation to these peptides was observed in 12/44 (27%) of the severe malaria cases, 13/55 (24%) of the uncomplicated malaria cases, and 18/50 (36%) of the healthy controls. Responses to individual peptide pools were limited. These studies confirm the presence of adaptive cell-mediated immunity to preerythrocytic malaria antigens in volunteers from Mali and demonstrate that suballeles of the HLA-A2 supertype can effectively present antigenic epitopes. However, whether these immune responses to TRAP, CSP, and Exp-1 malarial proteins play a substantial role in protection remains a matter of controversy.
authors.affiliation: The University of Maryland at Baltimore, Center for Vaccine Development, 685 W. Baltimore St., HSF 480, Baltimore, MD 21201, USA.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Lyke
authors.forename: Robin B
authors.initials: RB
authors.lastname: Burges
authors.forename: Yacouba
authors.initials: Y
authors.lastname: Cissoko
authors.forename: Lansana
authors.initials: L
authors.lastname: Sangare
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Kone
authors.forename: Modibo
authors.initials: M
authors.lastname: Dao
authors.forename: Issa
authors.initials: I
authors.lastname: Diarra
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernández-Vina
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
mesh_terms: D000293:Adolescent; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D000939:Epitopes; D015789:HLA-A2 Antigen; D007371:Interferon-gamma