Figure 2.

The interaction of mCRPs with the adaptive immune response: CD46, CD55, and CD59 all have known interactions with the adaptive immune response. This figure summarizes what is currently known about each of their interactions with adaptive responses, specifically T-cell responses. CD46 is known to be expressed on the surface of tumor cells and its binding to a naïve CD4+ T-cell in the presence of a secondary activation stimuli results in IFNγ and IL-2 production. Though initially immuno-stimulatory, as IL-2 accumulates it causes activated CD4+ T-cells to undergo a transformation into a Th1 Regulatory cell that produces high levels of IL-10. Two important aspects of CD55 activity are shown here. First, CD55 on the surface of T-cells are known to interact with CD97 displayed on the surface of Antigen Presenting Cells (APCs). This interaction leads to a shift in T-cell functionality, resulting in T-cells that function like TRegs and produce IL-10. The blockade of CD55 on the surface of T-cells has also revealed the immunosuppressive function of CD55. When CD55 is blocked on both CD4+ and CD8+ naïve T-cells followed by immune stimulation (in vitro) or immunization (in vivo), T-cells are shown to proliferate and to produce increased IFNγ, IL-2, and IL-4 and decreased IL-10 as compared to cells or animals that were untreated. This effect appears to be dependent on the increased levels of C3 and C5 present due to blocked functionality of CD55. In certain circumstances, CD59 is found to be overexpressed on CD4+ T-cells which results in downregulation of CD4+ activity. Accordingly, blockade of CD59 results in enhanced T cell responses consisting of increased cell proliferation, decreased IL-10 production and increased IFNγ production.