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Title

Generation and characterization of malaria-specific human CD8(+) lymphocyte clones: effect of natural polymorphism on T cell recognition and endogenous cognate antigen presentationby liver cells

Authors
Bonelo, A
Valmori, D
Champagne, P
Romero, J F
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Published in European Journal of Immunology. 2000, vol. 30, no. 11, p. 3079-88
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-gamma 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/K(b)-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.
Keywords AdultAnimalsAntigen Presentation/geneticsAntigens, Protozoan/genetics/immunologyCD8-Positive T-Lymphocytes/immunologyCell Differentiation/immunologyCytotoxicity, ImmunologicHumansLiver/immunologyMalaria/immunologyMicePlasmodium falciparum/immunologyPolymorphism, Genetic/geneticsReceptors, Antigen, T-Cell/genetics/immunology
Identifiers
PMID: 11093122
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Research groups Hépatologie chirurgicale (327)
Compatibilité tissulaire et transplantation clinique (562)
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BONELO, A et al. Generation and characterization of malaria-specific human CD8(+) lymphocyte clones: effect of natural polymorphism on T cell recognition and endogenous cognate antigen presentationby liver cells. In: European Journal of Immunology, 2000, vol. 30, n° 11, p. 3079-88. https://archive-ouverte.unige.ch/unige:41052

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Deposited on : 2014-10-21

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