HLA-DR-promiscuous T cell epitopes from Plasmodium falciparum pre-erythrocytic-stage antigens restricted by multiple HLA class II alleles

Previously, we identified and established the antigenicity of 17 CD8(+) T c ell epitopes from five P. falciparum Ags that are restricted by multiple co mmon 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-l, that bind between at least five a nd up to 11 different HLA-DR molecules representative of the most common HL A-DR Ags worldwide. These peptides recall lymphoproliferative and cytokine responses in immune individuals experimentally immunized with radiation-att enuated 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 th ree populations, and that the frequency and magnitude of helper T lymphocyt e 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), a nd mean frequencies of IFN-gamma responses are 66.3% (irradiated sporozoite s) vs 27.3% (Kenyan) vs 8.7% (Javanese). The identification of HLA class II degenerate T cell epitopes from P, falciparum validates our predictive str ategy in a biologically relevant system and supports the potential for deve loping a broadly efficacious epitope-based vaccine against malaria focused on a limited number of peptide specificities.