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

被引:127
作者
Doolan, DL
Southwood, S
Chesnut, R
Appella, E
Gomez, E
Richards, A
Higashimoto, YI
Maewal, A
Sidney, J
Gramzinski, RA
Mason, C
Koech, D
Hoffman, SL
Sette, A
机构
[1] USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA
[2] Epimmune, San Diego, CA 92121 USA
[3] USN, Med Res Unit 2, Jakarta, Indonesia
[4] USA, Med Res Unit, Nairobi, Kenya
[5] Kenya Med Res Inst, Nairobi, Kenya
关键词
D O I
10.4049/jimmunol.165.2.1123
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-l, 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.
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页码:1123 / 1137
页数:15
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