B7-H7 has T Cell Co-Stimulatory and Co-Inhibitory Effects

B7-H7 Can Mediate T Cell Co-stimulatory and Co-inhibitory Effects

B7-H7, also known as HHLA2, is the only member of the B7 family that is found in humans but not in mice. Unlike other B7 family members, B7-H7 has three extracellular immunoglobulin-like domains with an IgV-IgC-IgV arrangement. Similar to B7-H3, B7-H7 has been reported to have both co-stimulatory and co-inhibitory functions.¹ While B7-H7 on antigen-presenting cells (APCs) has been shown to bind to CD28H/TMIGD2 on naïve T cells and promote T cell proliferation and cytokine production, B7-H7 has also been shown to inhibit T cell proliferation and reduce cytokine secretion.^1-3 One explanation for these seemingly contradictory findings is that B7-H7 has two receptors with CD28H being a co-stimulatory receptor that is gradually lost during T cell activation, which allows a second, unidentified co-inhibitory receptor to become the preeminent B7-H7 receptor.³ B7-H7 is expressed in a number of human cancers and its expression typically correlates with metastasis and a poor prognosis, suggesting that tumor cell-expressed B7-H7 interacts with a B7-H7 co-inhibitory receptor expressed on
activated T cells to inhibit the anti-tumor immune response.⁴

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B7-H7 binding to CD28H delivers a T cell co-stimulatory signaling, but B7-H7 can also have T cell co-inhibitory effects.

B7-H7/HHLA2 can mediate T cell co-stimulatory effects by binding to CD28H/ TMIGD2 but may also mediate T cell co-inhibitory effects by binding to an unidentified receptor. B7-H7/HHLA2 is expressed on antigen-presenting cells (APCs) and binds to the T cell-expressed receptor, CD28H, to stimulate T cell proliferation and cytokine production. Conversely, B7-H7/HHLA2 has also been shown to function as a T cell co inhibitory molecule, suggesting that B7-H7/HHLA2 may interact with a second unidentified receptor that inhibits T cell activity.

Analysis of the binding response between R&D Systems Recombinant Human B7-H7 and Recombinant Human CD28H proteins.

B7-H7/HHLA2 Binds to CD28H/TMIGD2. Recombinant Human CD28H/TMIGD2 Fc Chimera (R&D Systems, Catalog # 8316-TR) was coated on a plate at 0.125 μg/mL and the indicated concentrations of Biotinylated Recombinant Human B7-H7/HHLA2 Fc Chimera (R&D Systems, Catalog # BT8084) were added. Recombinant Human B7-H7/HHLA2 bound with an ED₅₀ of 0.025-0.125 μg/mL.

Analysis of the effect of R&D Systems Recombinant Human B7-H7 Fc Chimera protein on IL-2 secretion by activated T cells.

B7-H7/HHLA2 Inhibits Anti-CD3-induced IL-2 Secretion by Human T Cells. Human T cells were incubated with an immobilized Mouse Anti-Human CD3 epsilon Monoclonal Antibody (R&D Systems, Catalog # MAB100) and the indicated concentrations of Recombinant Human B7-H7/HHLA2 Fc Chimera (R&D Systems, Catalog # 8084-B7).IL-2 secretion was measured in cell culture supernatants using the Human IL-2 Quantikine^TM ELISA Kit (R&D Systems, Catalog # D2050).The ED₅₀for this effect is typically 0.075-0.75 μg/mL in the presence of a Goat Anti-Human IgG Fc Polyclonal Antibody (R&D Systems, Catalog # G-102-C).