HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT

Parasite Immunol. 2000 Oct;22(10):501-14. doi: 10.1046/j.1365-3024.2000.00331.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-A2 Antigen / immunology*
  • Humans
  • Interferon-gamma / immunology*
  • Malaria, Falciparum / immunology*
  • Male
  • Peptides / immunology
  • Plasmodium falciparum / immunology


  • Antigens, Protozoan
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Peptides
  • Interferon-gamma