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B7 Family Ligands and CD28 Family Receptors

The B7 family ligands and the CD28 family receptors belonging to the immunoglobulin superfamily (IgSF) are essential in modulating immune responses. Most B7 ligands contain both Ig-like variable (V)-type and Ig-like constant (C)-type domains, whereas most CD28 receptor has only one Ig-like V-type domain ("IgV" and "IgC" as shown in the schematic diagram below). The IgV-type domains are usually responsible for interacting with their corresponding ligands or receptors.  Interactions between B7 ligands and CD28 receptors play a central role in regulating T cell response by eliciting both positive co-stimulatory and negative inhibitory signals.  B7 ligands are expressed on the surface of many cell types including antigen-presenting cells (APC), where they interact with CD28 family receptors on T cells to provide activating or inhibitory signals to regulate T cell activation and tolerance.  Some inhibitory B7 ligands such as PD-L1 and PD-L2 are also expressed on tumor cells, resulting in the suppression of immune response.  Therefore stimulating or neutralizing the interactions between B7 ligands and CD28 receptors hold great therapeutic potential. They constitute an important class of molecular targets for the development of novel therapeutic agents for human diseases, including autoimmune disorders and cancers.  

Among above these pathways, B7-1 (CD80) and B7-2 (CD86) ligands acting through their receptors, CD28 and CTLA4 (CD152), are the most extensively characterized.  Ligands B7-1 and B7-2 on antigen-presenting cells (APC) bind CD28 on resting T cells and transduce a major co-stimulatory signal to activate T cells.  After the initial activation, CTLA4 expression is induced on T cells and it engages the same B7-1 and B7-2 ligands to restrain CD28-mediated activating signals.  During the past decade, several new pathways have been discovered, including PD-L1/PD-L2/PD-1, ICOSL/ICOS, and B7-H4/BTLA.  PD-L1 and PD-L2 are two ligands for the receptor PD1, which mediates inhibitory pathways critical for maintaining self-tolerance and modulating the duration and amplitude of T cell-mediated immune responses. In contrast, ICOSL binds its receptor ICOS to activate a co-stimulatory pathway important for helper T cell differentiation and memory B cell development.  Interestingly some B7 family ligands show promiscuous binding behavior, e.g., ICOSL can also bind both CD28 and CTLA4 receptors, while PD-L1 can bind B7-1 ligand (see the diagram above). 

The receptors for the B7 family members, B7-H3 and B7-H5, have not been identified.  B7-H3 can bind activated T cells and produces both stimulatory and inhibitory effects.  B7-H4 also binds activate T cells but is thought to inhibit T cell function through the newly identified receptor, BTLA (CD272).  Myeloid-derived suppressor cells (MDSC) also express a receptor for B7-H4 and aberrant expression of B7-H4 is seen in many cancer types and often associates with poor prognosis.  Recently two new B7 family members, B7-H6 and B7-H7, have also been described.  B7-H6 binds the activating natural killer receptor NKp30 (CD337). However the physiological function of B7-H6 remain elusive.  B7-H7 can co-stimulate or inhibit T cell growth and cytokine production.  CD28H has been identified as a receptor for B7-H7 to transduce a co-stimulatory signal for T cell activation.  Collectively the spatially and temporally regulated expression of co-stimulatory and inhibitory B7 ligands provides the controls underlying T cell-mediated immune responses.

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B7 Family Ligands and CD28 Family Receptors Related Genes, Proteins and Antibodies

G&P Biosciences provide a comprehensive list of products and services for B7 family ligands and CD28 family receptors R&D.  We offer 100% sequence verified full-length cDNA clones for all known B7 ligands and CD28 receptors related genes as well as pre-packaged high-titer lentiviral particles.  The pre-packaged lentiviral particles are ready to transduce any mammalian cell types to generate stable expressing cell lines with the choice of multiple antibiotics selection markers available. We also offer highly purified recombinant proteins (either as a Fc-fusion or with a His-tag) for most B7 family ligands and CD28 family receptors.  Additionally we offer recombinant monoclonal antibodies that target B7 family ligands and CD28 family receptors with high affinity and specificity.  Many of these antibodies efficiently block B7 ligand/CD28 receptor-mediated inhibitory pathways or activate co-stimulatory pathways, therefore potently enhancing anti-tumor immunity in vitro and in vivo.      

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