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.
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.
Bonelo
A
A
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Valmori
D
D
Triponez
F
F
Tiercy
J M
JM
Mentha
G
G
Oberholzer
J
J
Champagne
P
P
Romero
J F
JF
Esposito
F
F
Nebié
I
I
Barbey
C
C
Romero
P
P
Herrera
S
S
Corradin
G
G
López
J A
JA
D000328:Adult; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008099:Liver / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D000953:Antigens, Protozoan; D011948:Receptors, Antigen, T-Cell