B7-CD28家族.docVIP

Ligand LigandExpression Receptor/Expression Function of Receptor on T Cells Implications for Human Disease B7-1 CD80 Inducible: APCs slower kinetics than B7-2 , T cells CD28Constitutive: mouse all T cells , human 95% of CD4+, 50% of CD8+ T cells , plasma cells, NK cells Stimulation of naive and previously activated T cells upon TCR ligation: ↑ proliferation ↓ p27Kip1,↑ G1/S ; ↑ cytokine production ↑ NFκB, ↑ IL2 ; ↑ survival ↑ Bcl-xL, ↑ survival of Tregs ; ↑ glucose metabolism; provides T cell-dependent B cell help for class switching. Blockade of pathway to treat autoimmune inflammatory diseases and for transplantation; active engagement to expand anti-tumor T cells and Tregs B7-2 CD86 Constitutive at low levels; inducible: APCs, T cells B7-1 Inducible: APCs slower kinetics than B7-2 , T cells CTLA-4 CD152 Inducible: T cells; constitutive: Tregs Inhibition of TCR-dependent activation: ↓ proliferation ↑ p27Kip1, ↓ G1/S ; ↓ cytokine production ↓ NFκB, ↓ IL2 ; CD28- dependent and -independent functions; promotes inhibitory function of Tregs. Blockade of pathway in tumor immunotherapy; receptor polymorphisms linked with autoimmunity B7-2 Constitutive at low levels; inducible: APCs, T cells ICOS Ligand B7-H2, CD275 Induced by TNFα and IFNγ: APCs, T cells, fi broblasts, endothelium ICOS CD278 Inducible: T cells CD28- dependent and CD28- independent ; constitutive: resting memory T cells, Tregs ICOS CD278 Inducible: T cells CD28- dependent and CD28- independent ; constitutive: resting memory T cells, Tregs Receptor polymorphisms associated with immunodefi ciency and autoimmunity PD-L1 B7-H1, CD274 Constitutive mouse , induced by IFNα/β/γ: APCs, T cells, nonhematopoieitic cells; overexpressed in tumor cells PD1 CD279 Inducible: DCs, macrophages, placenta human ; overexpressed in tumor cells Inhibition: ↓ TCR signals through recruitment of protein tyrosine phosphatases most effective at low levels of TCR signaling ; ↓ cytokine product