CD4 T cells from malaria-nonexposed individuals respond to the CD36-Binding Domain of Plasmodium falciparum erythrocyte membrane protein-1 via an MHC class II-TCR-independent pathway.
We have studied the human CD4 T cell response to a functionally conserved domain of Plasmodium falciparum erythrocyte membrane protein-1, cysteine interdomain region-1alpha (CIDR-1alpha). Responses to CIDR-1alpha were striking in that both exposed and nonexposed donors responded. The IFN-gamma response to CIDR-1alpha in the nonexposed donors was partially independent of TCR engagement of MHC class II and peptide. Contrastingly, CD4 T cell and IFN-gamma responses in malaria-exposed donors were MHC class II restricted, suggesting that the CD4 T cell response to CIDR-1alpha in malaria semi-immune adults also has a TCR-mediated component, which may represent a memory response. Dendritic cells isolated from human peripheral blood were activated by CIDR-1alpha to produce IL-12, IL-10, and IL-18. IL-12 was detectable only between 6 and 12 h of culture, whereas the IL-10 continued to increase throughout the 24-h time course. These data strengthen previous observations that P. falciparum interacts directly with human dendritic cells, and suggests that the interaction between CIDR-1alpha and the host cell may be responsible for regulation of the CD4 T cell and cytokine responses to P. falciparum-infected erythrocytes reported previously.
Ndungu
Francis M
FM
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
Sanni
Latifu
L
Urban
Britta
B
Stephens
Robin
R
Newbold
Christopher I
CI
Marsh
Kevin
K
Langhorne
Jean
J
D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D037181:Lectins, C-Type; D008288:Malaria / Q000378:metabolism / Q000469:parasitology; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018955:CD36 Antigens; D003545:Cysteine; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D037181:Lectins, C-Type; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C085731:erythrocyte membrane protein 1, Plasmodium falciparum