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Checkpoint Proteins

Protein Name Species Fusion Tag Catalog Code Interacting protein
B7-H2 Mouse Mouse IgG1 Fc M096E ICOS
B7-H2 Mouse Mouse IgG2a Fc M096F ICOS
B7-H2 Human Mouse IgG2a Fc P096F ICOS
B7-H3 Human Mouse IgG2a Fc P105F Not known
CD28 Human Mouse IgG2a Fc P090F CD80, CD86
CD86 Human Mouse IgG2a Fc P093F CD28, CTLA-4
CTLA-4 Human Mouse IgG2a Fc P095F CD80, CD86
CTLA-4 Human Mouse IgG2a aglyco-Fc P095G CD80, CD86
PD-1 Human Mouse IgG2a Fc P099F PD-L1, PD-L2
PD-1 Human Mouse IgG2a aglyco-Fc P099G PD-L1, PD-L2
PD-L1 Human Mouse IgG2a Fc P101F PD-1
PD-L1 Human Mouse IgG2a aglyco-Fc P101G PD-1
PD-L2 Human Mouse IgG2a Fc P103F PD-1
PD-L2 Human Mouse IgG2a aglyco-Fc P103G PD-1

Checkpoint Proteins are made of at least 7 ligands and 5 receptors. The redundancy in the interaction specificity between ligands and receptors are reminiscent of the TNF superfamily. For example, B7-1 interacts with both CD28 and CTLA-4, yet these interactions deliver stimulatory and inhibitory signals, respectively. Collectively this family of molecules are called co-stimulatory proteins, yet they deliver both positive and negative signals. In addition, even though the “ligand” proteins have relatively short cytoplasmic tails, it appears they are also capable of deliver the “inward” signaling upon interaction with their respective receptors.

The revelation of the bi-directional signaling capacities of the B7/CD28 proteins blurs the line between ligand and receptor of this family proteins. Though all receptors interact with the ligands within the structurally related Ig superfamily (IgSF), except for BTLA which interacts with both B7-H4 and HVEM, the latter being a member of the TNF receptor superfamily (TNFRSF). The functional studies on B7/CD28 superfamily proteins have shown that they not only promote the initial T cell activation, but also regulate the self-tolerance by supporting CD4+CD25+Treg for the homeostasis. Importantly, CTLA-4 exerts the inhibitory effects via both B7-1/B7-2 dependent and independent fashions. The newer members of the B7 family, ICOSL, PD-L1, PD-L2, B7-H3, and B7-H4 can express on both professional APCs and cells of non-lymphoid organs, hence, providing novel mechanism for regulating T cell activation and tolerance in peripheral tissues. ICOS/ICOSL and B7-1/B7-2 pathways are synergistic for promoting T-dependent antibody responses, yet ICOS/ICOSL axis only stimulates the T cell effector function but not T cell expansion. Engagement of PD-1 with its ligand (PD-L1 and PD-L2) triggers inhibitory signals, diminishes cell proliferation and cytokine production. The PD-1/PDL1/PDL2 axis is widely regarded to play critical roles in failed antitumor immunity and are therefore under rigor investigations for developing oncological therapeutics.

Our B7/CD28 Ig-Fc fusion proteins are homodimers linked by a pair of disulfide bonds at the hinge region of mouse IgG2a, affinity purified and size-excluded to homogeneity