Figure 2.

T cell activation or deactivation requires three signals from DCs. (A) T cell activation requires signal 1 in the form of TCR interacting with antigen-MHC complex which is key in innating downward signaling through ITAMs. Interaction of co-stimulatory molecules (interaction of CD40-CD40L, and CD80/86-CD28) form part of signal 2 as they work in tandem with TCR-antigen-MHC complex to enhance TCR signaling and initiate T cell proliferation. Signal 3 comes from DCs in the form of cytokines, and in CD4 T cells it is key in dictating which subset it will differentiate into. (B) Co-inhibitory molecules also form part of the second signal but unlike co-stimulatory molecules they inhibit TCR signaling, thus dampening immune responses. Interaction of PD-1 with PD-L1 inhibits T cell activation, while CTLA4 competes for binding with CD28 to CD80/86 and successful binding of CTLA4 to CD80/86 nullifies CD28-CD80/86 activation signal. Malaria has been shown to induce expression of PD-1, LAG3 and CTLA-4 on CD4 T cells, and this inhibits the activation signal from DCs (Figure was created using BioRender).