Figure 1.

Model for Vγ9Vδ2 γδ T cell response to Plasmodium falciparum. Vγ9Vδ2 γδ T cells recognize soluble phosphoantigens released from schizont stage parasites and potentially other iRBC stages. Though precise mechanisms of antigen presentation and recognition remain unclear, phosphoantigens are likely presented to Vγ9Vδ2 TCR via BTN3A1. Other signals, such as CD28 and IL-2 from CD4+ cells and IL-15 from myeloid cells, contribute to Vγ9Vδ2 proliferation and anti-parasitic activity, while Vγ9Vδ2 anti-parasitic activity is dependent on granulysin production. Following activation, Vγ9Vδ2 cells likely influence myeloid cell differentiation and activation through production of myeloid growth factors, and can themselves develop antigen-presenting cell (APC)-like functions such as activation of CD4+ T cells and cross-presentation of antigen to CD8+ T cells. After repeated parasite exposure, cells decrease production of pro-inflammatory cytokines and increase expression of CD16 and immunoregulatory molecules such as Tim-3. CD16 expression may enable alterative functions, such as antibody-dependent cellular cytotoxicity (ADCC). Immune cell images are adapted from the Reactome Icon Library (49).