Fig. 3.
Ligand-mediated lymphocyte control. a Two signals are needed for naive T cell activation: Firstly, CD80 (B7-1) or CD86 (B7-2) has to trigger CD28 signaling, and secondly, the T cell receptor has to interact with the respective peptide/MHC complex. Shortly after activation, CTLA-4 is up-regulated on the T cell-surface competing with CD28 for ligand binding and in turn delivers an inhibitory signal to the T cell. b PD-1 is an inhibitory receptor on activated T cells. Its ligands PDL1 and PDL2 can be expressed on peripheral tissues during inflammation, but also on tumor cells. c In contrast, NKG2D is an activating receptor on NK cells and delivers a co-stimulatory signal to cytotoxic cells (CTLs). Human ligands induced by viral infection, cytokines, or DNA damage are MICA, MICB, and the ULBP1–6. Shedding of these ligands (sNKG2DL) by tumor cells leads to NKG2D receptor internalization thereby preventing their activating effect