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Infection and Immunity, September 2005, p. 5799-5808, Vol. 73, No. 9
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.9.5799-5808.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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
Kirsten E. Lyke,1 Robin B. Burges,1 Yacouba Cissoko,2 Lansana Sangare,2 Abdoulaye Kone,2 Modibo Dao,2 Issa Diarra,2 Marcelo A. Fernández-Vi
a,3
Christopher V. Plowe,1
Ogobara K. Doumbo,2 and
Marcelo B. Sztein1*
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF I 480, Baltimore, Maryland 21201,1 Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, BP 1805 Point G, Bamako, Mali,2 C. W. Bill Young/Department of Defense Marrow Program, Naval Medical Research Center, Georgetown University, Kensington, Maryland3
Received 13 October 2004/ Returned for modification 1 February 2005/ Accepted 25 April 2005
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.
* Corresponding author. Mailing address: The University of Maryland at Baltimore, Center for Vaccine Development, 685 W. Baltimore St., HSF 480, Baltimore, MD 21201. Phone: (410) 706-2345. Fax: (410) 706-6205. E-mail: msztein{at}medicine.umaryland.edu.
Infection and Immunity, September 2005, p. 5799-5808, Vol. 73, No. 9
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.9.5799-5808.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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