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 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, ex...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 165; no. 2; pp. 1123 - 1137
Main Authors:	Doolan, Denise L, Southwood, Scott, Chesnut, Robert, Appella, Ettore, Gomez, Eduardo, Richards, Allen, Higashimoto, Yuichiro I, Maewal, Ajesh, Sidney, John, Gramzinski, Robert A, Mason, Carl, Koech, Davy, Hoffman, Stephen L, Sette, Alessandro
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 15-07-2000
Subjects:	Adolescent Adult Aged Alleles Amino Acid Motifs - genetics Amino Acid Motifs - immunology Amino Acid Sequence Animals Antigens, Protozoan - metabolism Cells, Cultured circumsporozoite protein Conserved Sequence Cytokines - biosynthesis Epitopes, T-Lymphocyte - metabolism Erythrocytes - immunology Erythrocytes - parasitology exported protein 1 Female Gene Frequency - immunology histocompatibility antigen HLA Histocompatibility Testing HLA-DR Antigens - biosynthesis HLA-DR Antigens - genetics HLA-DR Antigens - metabolism Humans Immunity, Innate Immunologic Memory Indonesia Kenya liver-stage antigen 1 Lymphocyte Activation - genetics Malaria Vaccines - administration & dosage Malaria Vaccines - immunology Malaria, Falciparum - genetics Malaria, Falciparum - immunology Malaria, Falciparum - transmission Male Middle Aged Molecular Sequence Data Peptide Fragments - immunology Peptide Fragments - metabolism Plasmodium falciparum Plasmodium falciparum - growth & development Plasmodium falciparum - immunology Plasmodium falciparum - metabolism Protein Binding - genetics Protein Binding - immunology sporozoite surface protein 2 T-Lymphocytes, Helper-Inducer - immunology Vaccines, Attenuated - administration & dosage Vaccines, Attenuated - immunology Kenya Indonesia
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Summary:	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-gamma 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.165.2.1123