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*
Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910;
Epimmune, San Diego, CA 92121;
Naval Medical Research Unit 2, Jakarta, Indonesia;
§
U.S. Army Medical Research Unit-Kenya, Nairobi, Kenya; and
¶
Kenya Medical Research Institute, Nairobi, Kenya
Previously, we identified and established the antigenicity of 17
CD8+ T cell epitopes from five P. falciparum
Ags that are restricted by multiple common HLA class I alleles. Here,
we report the identification of 11 peptides from the same Ags,
cicumsporozoite protein, sporozoite surface protein 2, exported
protein-1, and liver-stage Ag-1, that bind between at least five and up
to 11 different HLA-DR molecules representative of the most common
HLA-DR Ags worldwide. These peptides recall lymphoproliferative and
cytokine responses in immune individuals experimentally immunized with
radiation-attenuated Plasmodium falciparum sporozoites
(irradiated sporozoites) or semi-immune individuals naturally exposed
to malaria in Irian Jaya or Kenya. We establish that all peptides are
recognized by individuals of each of the three populations, and that
the frequency and magnitude of helper T lymphocyte responses to each
peptide is influenced by the intensity of exposure to P.
falciparum sporozoites. Mean frequencies of lymphoproliferative
responses are 53.2% (irradiated sporozoites) vs 22.4% (Kenyan) vs
5.8% (Javanese), and mean frequencies of IFN-
responses are 66.3%
(irradiated sporozoites) vs 27.3% (Kenyan) vs 8.7% (Javanese). The
identification of HLA class II degenerate T cell epitopes from
P. falciparum validates our predictive strategy in a
biologically relevant system and supports the potential for developing
a broadly efficacious epitope-based vaccine against malaria focused on
a limited number of peptide specificities.
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