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Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.

Identifieur interne : 004031 ( Main/Exploration ); précédent : 004030; suivant : 004032

Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.

Auteurs : U. Blum-Tirouvanziam [Suisse] ; C. Servis ; A. Habluetzel ; D. Valmori ; Y. Men ; F. Esposito ; L. Del Nero ; N. Holmes ; N. Fasel ; G. Corradin

Source :

RBID : pubmed:7535817

Descripteurs français

English descriptors

Abstract

Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.

PubMed: 7535817


Affiliations:


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Le document en format XML

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<term>Epitopes</term>
<term>HLA-A2 Antigen (immunology)</term>
<term>Humans</term>
<term>Immunity, Cellular</term>
<term>Interferon-gamma (biosynthesis)</term>
<term>Lymphocyte Activation</term>
<term>Malaria, Falciparum (immunology)</term>
<term>Mice</term>
<term>Mice, Transgenic</term>
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<term>Peptides (immunology)</term>
<term>Peptides (metabolism)</term>
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<term>Protein Binding</term>
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<term>Animaux</term>
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<term>Cytotoxicité immunologique</term>
<term>Données de séquences moléculaires</term>
<term>Humains</term>
<term>Immunité cellulaire</term>
<term>Interféron gamma (biosynthèse)</term>
<term>Liaison aux protéines</term>
<term>Lymphocytes T (immunologie)</term>
<term>Paludisme à Plasmodium falciparum (immunologie)</term>
<term>Peptides ()</term>
<term>Peptides (immunologie)</term>
<term>Peptides (métabolisme)</term>
<term>Plasmodium falciparum (immunologie)</term>
<term>Protéines de protozoaire (immunologie)</term>
<term>Souris</term>
<term>Souris transgéniques</term>
<term>Séquence d'acides aminés</term>
<term>Épitopes</term>
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<div type="abstract" xml:lang="en">Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.</div>
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