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-1α (CIDR-1α). Responses to CIDR-1α were striking in that both exposed and nonexposed donors responded. The IFN-γ response to CIDR-1α in the nonexposed donors was partially independent of TCR engagement of MHC class II and peptide. Contrastingly, CD4 T cell and IFN-γ responses in malaria-exposed donors were MHC class II restricted, suggesting that the CD4 T cell response to CIDR-1α 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-1α 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-1α and the host cell may be responsible for regulation of the CD4 T cell and cytokine responses to P. falciparum-infected erythrocytes reported previously.