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The B7-CD28 Families of Immune Checkpoint Proteins

The B7 family of proteins consists of ten surface glycoproteins, B7-1/CD80, B7-2/CD86, B7-H1/PD-L1, B7-DC/PD-L2, B7-H2/ICOS L, B7-H3, B7-H4, B7-H5/VISTA, B7-H6, and B7-H7/HHLA2. B7 family proteins are expressed on antigen-presenting cells and regulate T cell activation by interacting with T cell-expressed immune receptors belonging to the CD28 family, which includes CD28, CTLA-4, PD-1, ICOS, BTLA, and CD28H. These interactions serve as antigen-independent, secondary signals that either promote or inhibit T cell activation, following recognition of the antigenic peptide/major histocompatibility complex (MHC) by the T cell receptor (TCR).

As the world’s leading developer and manufacturer of recombinant proteins, Bio-Techne offers a comprehensive range of R&D Systems™ bioactive B7-CD28 family proteins in a variety of different species with Fc or His tags, as well as an expanding line of Avi-tag biotinylated proteins for studying the most common therapeutic targets like PD-1 and CTLA-4, and potential next generation immuno-oncology targets. Our catalog also includes human and mouse antibodies for detecting B7 and CD28 family proteins and DuoSet™ ELISA Development Systems for detecting soluble human B7-H1, B7-H2, B7-H3, B7-H5, B7-H6, PD-1, and PD-L1. Find products for the molecules that you are interested in by clicking on the links in the table below.

Interactions between B7 and CD28 Family Proteins Regulate T Cell Activity

Interactions between members of the B7 and CD28 family proteins transduce either co-stimulatory or co-inhibitory secondary signals that regulate T cell activation.

Interactions between the B7 and CD28 family proteins regulate T cell activation. T cell activation requires two signals: 1) recognition of the antigenic peptide/major histocompatibility complex (MHC) by the T cell receptor (TCR) and 2) antigen-independent co-stimulation induced by interactions between co-signaling molecules expressed on antigen-presenting cells (APCs) and their T cell-expressed receptors. The B7 family proteins are co-signaling molecules, expressed on antigen-presenting cells (APCs) or tumor cells, that interact with T cell-expressed immune receptors belonging to the CD28 family to transduce either co-stimulatory or co-inhibitory signals that regulate T cell activation (Signal 2).

B7-CD28 Family Ligand-Receptor Interactions

B7-1, B7-2, CD28, and CTLA-4

B7-1/CD80 and B7-2/CD86 mediate T cell co-stimulatory or co-inhibitory effects by binding to either CD28 or CTLA-4, respectively. CTLA-4 blockade is one of the primary strategies that has been pursued for cancer immunotherapy.

PD-L1, PD-L2, and PD-1

PD-1 binding to either PD-L1 or PD-L2 interferes with early TCR/CD28 signaling and inhibits IL-2 production and T cell proliferation, T cell effector functions, and T cell survival. Blocking the functions of PD-1 or PD-L1 has been shown to boost the anti-tumor immune response in many different types of human cancer.

B7-H2 and ICOS

The interaction of B7-H2/ICOS L with T cell-expressed ICOS delivers a T cell co-stimulatory signal that enhances Th1 and Th2 cytokine production. Conversely, ICOS L/ICOS signaling may also promote the development and activity of regulatory T cells, contributing to the suppression of anti-tumor immune responses.

B7-H3

B7-H3 has been reported to be expressed in several human tumors and its expression typically correlates with a poor prognosis. Similar to B7-1 and B7-2, B7-H3 has been suggested to bind to more than one receptor, one that stimulates T cell activity and one that inhibits T cell activity.

B7-H4

B7-H4 is highly expressed on various tumor cell types and tumor-associated macrophages. Current research suggests that it binds to an unidentified receptor expressed on activated T cells and inhibits T cell proliferation and effector functions.

B7-H5/VISTA/PD-1H

B7-H5 is expressed on both antigen-presenting cells and T cells and has been shown to function as both a T cell co-inhibitory ligand and receptor. Multiple studies suggest that B7-H5/VISTA is involved in regulating anti-tumor immunity.

B7-H6 and NKp30

Expression of B7-H6 is induced under inflammatory conditions and B7-H6 overexpression is frequently observed in tumors. Although B7-H6 binds to NKp30, an activating receptor on natural killer cells, high level expression of B7-H6 in tumor tissues is commonly associated with tumor progression.

B7-H7 and CD28H

B7-H7/HHLA2 can stimulate T cell proliferation and cytokine production by binding to CD28H/TMIGD2, but may also mediate T cell co-inhibitory effects through its interaction with an unidentified receptor.

BTLA, HVEM, LIGHT

HVEM serves as a molecular switch regulating both T cell co-inhibitory and co-stimulatory signaling. Binding of HVEM to T cell-expressed BTLA or CD160 delivers a T cell inhibitory signal, while HVEM also has the ability to stimulate the effector functions of immune cells on which it is expressed by binding to LIGHT or Lymphotoxin-alpha.