Proposed model for the function of B7 family of costimulatory ligands. 1. B7-1/B7-2 and CD28/cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) regulate the clonal composition of naive T cells that become activated by antigen-bearing dendritic cells (DCs) migrating into the lymphoid organs from the peripheral tissues. 2. After clonal expansion of naive T cells, inducible costimulatory molecule (ICOS)–B7h promotes the T-dependent antibody isotype switching and expansion of effector T cells when the differentiated T helper cells (Th) migrate into the follicles and help to activate germinal-centre B cells. 3. Effector T cells (Teff) trafficking into inflamed tissues interact with antigen-presenting cells such as macrophages and are regulated by programmed death (PD)-1 and its ligands (PDLs). 4. B7-H3 and B7x could be the last-ditch regulators and control the interaction between Teff and the peripheral tissues. BTLA, B and T lymphocyte attenuator.