Figure 1. The B7/CD28 family interactions and their function outcomes.

The B7/CD28 family members are characterized by their common immunologlobulin extracellular binding domains, and their signaling pathways are driven mainly by their intracellular, tyrosine-containing motifs. In addition to the specific antigen–dependent signal provided by the MHC-antigen complex to the TCR, the cell-surface interactions involving the B7/CD28 family of cosignaling molecules provide a second signal to T cells to enhance or inhibit the TCR signal, which influences the proliferative capacity and functional fate of the T cell. In addition to CD28 ligation by B7-1 and B7-2, T cell costimulation can be mediated by ligation of inducible costimulator (ICOS) via its ligand ICOS-L or can be mediated by ligation of the newly reported trim-like transcript 2 (TLT-2) via its ligand B7-H3. Also, in addition to CTLA-4, BTLA, CD160, and PD-1, which exert their effects via ligation by their respective ligands, is a new molecule referred to as butyrophilin/B7-like molecule (BTNL2), a coinhibitory molecule that mediates signaling of activator protein 1 (AP1) and nuclear factor of activated T cells (NFAT) via a ligand that remains elusive (as indicated by a question mark). Costimulatory interactions are shown in green, coinhibitory interactions in red. TREMR, triggering receptors expressed on myeloid cells receptor. Adapted with permission from Cell (21).