HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.
The role of antigen specific CD8+ T-lymphocytes in mediating protection against sporozoite-induced malaria has been well established in murine models. In humans, indirect evidence has accumulated suggesting a similar protective role for antigen-specific CD8+ T-lymphocytes. Nevertheless, the low frequency of circulating specific cells together with the lack of sensitive methods to quantify them has hampered the direct assessment of their function. Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides. In addition to confirming the response to already described epitopes, we also identified five new CD8+ T-lymphocyte epitopes. These epitopes are presented in pre-erythrocytic stages gene products of Plasmodium falciparum 7G8 strain and correspond to the following protein segments: circumsporozoite (CS) 64-72, 104-113, 299-308 and 403-411; liver stage antigen (LSA-1) repeat region; sporozoite surface protein 2 or thrombospondin related anonymous protein (SSP2/TRAP) 78-88 and 504-513. Four of these peptides are conserved amongst all published sequences of P. falciparum strains. We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines.
González
J M
JM
Instituto de Inmunología del Valle, Universidad del Valle, Cali, Colombia.
Peter
K
K
Esposito
F
F
Nebié
I
I
Tiercy
J M
JM
Bonelo
A
A
Arévalo-Herrera
M
M
Valmori
D
D
Romero
P
P
Herrera
S
S
Corradin
G
G
López
J A
JA
D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010455:Peptides; D007371:Interferon-gamma