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Scientific article
English

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

Published inEuropean Journal of Immunology, vol. 30, no. 11, p. 3079-3088
Publication date2000
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
  • Adult
  • Animals
  • Antigen Presentation/genetics
  • Antigens, Protozoan/genetics/immunology
  • CD8-Positive T-Lymphocytes/immunology
  • Cell Differentiation/immunology
  • Cytotoxicity, Immunologic
  • Humans
  • Liver/immunology
  • Malaria/immunology
  • Mice
  • Plasmodium falciparum/immunology
  • Polymorphism, Genetic/genetics
  • Receptors, Antigen, T-Cell/genetics/immunology
Citation (ISO format)
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. 3079–3088. doi: 10.1002/1521-4141(200011)30:11<3079::AID-IMMU3079>3.0.CO;2-7
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Article (Published version)
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ISSN of the journal0014-2980
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