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Infect Immun, August 1998, p. 3579-3590, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mapping of Specific and Promiscuous HLA-DR-Restricted T-Cell Epitopes on the Plasmodium falciparum 27-Kilodalton Sexual Stage-Specific Antigen

Carmen E. Contreras,1 dagger Isabelle N. Ploton,1 Robert F. Siliciano,2 Christopher L. Karp,1 2 Raphael Viscidi,3 and Nirbhay Kumar1 *

Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health,1 and Departments of Medicine2 and Pediatrics,3 School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205

Received 17 December 1997/Returned for modification 6 March 1998/Accepted 6 May 1998

We have characterized HLA-DR-restricted T-cell epitopes on the 27-kDa protein (Pfg27), a sexual stage-specific antigen, of the human malaria parasite Plasmodium falciparum in subjects with a history of malaria. Pfg27, expressed early in the sexual stages, is recognized by monoclonal antibodies capable of reducing the infectivity of gametocytes in mosquitoes. By using 16 Pfg27-specific CD4+-T-cell clones derived from three donors, seven different T-cell epitopes were identified. Among them, P11 (amino acids 191 to 210 of the Pfg27 sequence, IDVVDSYIIKPIPALPVTPD) was found to contain a previously described binding motif for multiple HLA-DR allotypes. Indeed, P11 was found to be promiscuous in that it could be recognized by T cells in the context of at least five different HLA-DR molecules. The cytokine profile of the clones was mixed. Seven of nine T-cell clones exhibited a Th0-like cytokine profile, producing high levels of gamma interferon (IFN-gamma ) and interleukin-4 (IL-4) upon stimulation with specific peptides and mitogens. The other two clones had a Th1-like cytokine profile with high expression of IFN-gamma and no IL-4. Identification of a promiscuous epitope in Pfg27 could play a significant role in the design of a subunit vaccine for suppressing malaria transmission.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Hygiene and Public Health, 615 N. Wolfe St., Baltimore MD 21205. Phone: (410) 955-7177. Fax: (410) 955-0105. E-mail: nkumar{at}jhsph.edu.

dagger Present address: Medicina Inst. de Immunologia, University of Venezuela, Caracas, Venezuela.

Infect Immun, August 1998, p. 3579-3590, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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