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.

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.

• Authors: A Bonelo, D Valmori, F Triponez, J M Tiercy, G Mentha, J Oberholzer, P Champagne, J F Romero, F Esposito, I Nebié, C Barbey, P Romero, S Herrera, G Corradin, J A López
• Journal: European journal of immunology (Eur J Immunol) Vol. 30 Issue 11 Pg. 3079-88 (Nov 2000) ISSN: 0014-2980 [Print] Germany
• PMID: 11093122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Receptors, Antigen, T-Cell

Topics

• 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)