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  • Generation and characterization of malaria specific human CD8+ lymphocyte clones: Effect of natural polymorphism on T cell recognition and on the recognition of cognate antigen endogenously presented by liver cells

    Author(s)
    Bonelo, A
    Valmori, D
    Triponez, F
    Tiercy, JM
    Mentha, G
    Oberholzer, J
    Champagne, P
    Romero, JF
    Esposito, F
    Nebie, I
    Barbey, C
    Romero, P
    Herrera, S
    Corradin, G
    Lopez, JA
    Griffith University Author(s)
    Lopez Ramirez, Alejandro
    Year published
    2000
    Metadata
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    Abstract
    CD8+ cytolytic T lymphocytes (CTL) play a fundamental role in the clearance of malaria parasites from the liver in mouse models. In humans, however, only low levels of parasite-specific CD8+ T lymphocytes have been observed in individuals living in endemic areas. In the present study, we identified high levels of circulating CD8+ T lymphocytes specific for a previously described HLA-A2-restricted CTL epitope of the circumsporozoite (CS) protein of Plasmodium falciparum in an adult living in Burkina Faso, as evidenced by IFN- + ELISPOT assay and MHC-tetramer technology. After cloning by limiting dilution culture, T cell ...
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    CD8+ cytolytic T lymphocytes (CTL) play a fundamental role in the clearance of malaria parasites from the liver in mouse models. In humans, however, only low levels of parasite-specific CD8+ T lymphocytes have been observed in individuals living in endemic areas. In the present study, we identified high levels of circulating CD8+ T lymphocytes specific for a previously described HLA-A2-restricted CTL epitope of the circumsporozoite (CS) protein of Plasmodium falciparum in an adult living in Burkina Faso, as evidenced by IFN- + ELISPOT assay and MHC-tetramer technology. After cloning by limiting dilution culture, T cell recognition of natural CS variants of P. falciparum was studied. The results demonstrate that naturally occurring variations drastically affect residues critical for T cell recognition as only two out of nine sequences analyzed were efficiently recognized by the CTL clones. These clones were also used to analyze T cell recognition of the endogenously presented cognate antigen. We observed efficient antigen recognition of both HLA-A*0201-transfected murine antigen presenting cells and liver cells from HLA-A*0201/Kb-transgenic mice upon infection with recombinant vaccinia virus encoding the CS protein (WR-CS). More importantly, we demonstrate for the first time efficient recognition of WR-CS-infected human liver cells.
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    Journal Title
    European Journal of Immunology
    Volume
    30
    Issue
    11
    DOI
    https://doi.org/10.1002/1521-4141(200011)30:11<3079::AID-IMMU3079>3.0.CO;2-7
    Subject
    Cellular Immunology
    Immunology
    Publication URI
    http://hdl.handle.net/10072/55245
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    • Journal articles

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