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)
Year published
2000
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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
Subject
Cellular Immunology
Immunology