Emerging Co-signaling Networks in T Cell Immune Regulation

Co-signaling molecules are surface glycoproteins that positively or negatively regulate the T cell response to antigen. Co-signaling ligands and receptors crosstalk between the surfaces of antigen-presenting cells (APCs) and T cells, and modulate the ultimate magnitude and quality of T cell receptor (TCR) signaling. In the past 10 years, the field of co-signaling research has been advanced by the understanding of underlying mechanisms of the immune modulation led by newly identified co-signaling molecules and the successful preclinical and clinical trials targeting co-inhibitory molecules called immune checkpoints in the treatment of autoimmune diseases and cancers. In this review, we briefly describe the characteristics of well-known B7 co-signaling family members regarding the expression, functions and therapeutic implications and to introduce newly identified B7 members such as B7-H5, B7-H6, and B7-H7. [Immune Network 2013;13(5):184-193] Receptor B7.1 (CD80) IgVIgC Co-stimulation CD28 Co-inhibition CTLA-4 (CD152) Co-inhibition B7-H1 (CD274) B7.2 (CD86) IgVIgC Co-stimulation CD28 Co-inhibition CTLA-4 B7-H1 (PD-L1, CD274) IgVIgC Co-inhibition PD-1 (CD279) Co-inhibition B7.1 Co-stimulation Unknown B7-DC (PD-L2, CD273) IgVIgC Co-inhibition PD-1 B7-H2 (ICOSL, CD275) IgVIgC Co-stimulation ICOS (CD278) Co-stimulation CD28 B7-H3 (CD276) IgVIgCIgVIgC (Hu) Co-stimulation Unknown IgVIgC (Mo) Co-inhibition Unknown B7-H4 (VTCN1) IgVIgC Co-inhibition Unknown B7-H5 (VISTA) IgV Co-inhibition Unknown B7-H6 (NCR3LG1) IgVIgC Co-stimulation NKp30 B7-H7 (HHLA2) IgVIgCIgV Co-stimulation CD28H