The CTLA-4/CD28-CD80/CD86 and TIGIT/CD226-CD112/CD155 networks both consist of an inhibitory (CTLA-4 and TIGIT) and a stimulatory (CD28 and CD226) receptor on T cells and two ligands expressed on APCs. In addition to APCs, CD155 is also expressed on tissues and tumor cells. PD-1 has two receptors: PD-L1, which is expressed on APCs and on a variety of tissues, and PD-L2, which is found on APCs. Tim-3 binds to galectin 9 expressed on hematopoietic cells and non-hematopoietic tissues. Lines indicate protein-protein interactions; − represents inhibition, + represents activation.