The activation state of T cells is dependent upon the integration of signals derived from the T cell receptor (TCR) complex through antigen presentation, and secondary co-stimulatory or co-inhibitory signals delivered by members of the B7 family. For instance, a classical co-stimulatory response is initiated by B7-1 or B7-2 engagement of the T cell receptor CD28. These same ligands may also stimulate a co-inhibitory signal via binding the receptor CTLA4. Other members of the B7 family have differential effects on T cell activities including modulating cytokine production (Figure 1) and/or proliferation rates (Figure 2).
R&D Systems offers a wide range of tools to study members of the B7 family and their receptors including active proteins, antibodies, and ELISAs (see R&D Systems co-stimulation/inhibition products).
Figure 1. The production of inflammatory cytokines in the supernatant of PHA-activated human T cells is stimulated by CD3-activation (anti-CD3; 500 ng/mL) and differentially affected by supplementation with R&D Systems recombinant human B7 family proteins: B7-1/Fc (Catalog # 140-B1; 1 µg/mL), B7-2/Fc (Catalog # 141-B2; 1 µg/mL), B7-H2/Fc (Catalog # 165-B7; 1 µg/mL), PD-L2/Fc (Catalog # 1224-PL; 10 µg/mL) and B7-H3 (4Ig)/B7-H3b (Catalog # 2318-B3; 10 µg/mL). Cytokines were measured using R&D Systems human Quantikine ELISA Kits (IL-2, Catalog # D2050; IFN-gamma, Catalog # DIF50; TNF-alpha, Catalog # DTA00C; IL-10, Catalog # D1000B). IL-10 levels are on a different scale and are shown in the inset.
Figure 2. B7 family members differentially affect proliferation rates in PHA-activated human T cells. T cells proliferate in response to sub-optimal CD3 activation (anti-CD3; 20 ng/mL) when co-stimulated with R&D Systems recombinant human B7-H2/Fc (Catalog # 165-B7; 3 µg/mL). This effect is inhibited by blocking B7-H2 interaction with its cellular receptor ICOS by adding R&D Systems human recombinant ICOS/Fc (Catalog # 169-CS; 8 µg/mL). Proliferation is stimulated by anti-CD3 (500 ng/mL) alone and is enhanced by co-stimulation with R&D Systems recombinant human B7-1/Fc (Catalog # 140-B1; 1.2 µg/mL). In contrast, anti-CD3-induced proliferation is suppressed by adding R&D Systems recombinant human PD-L2/Fc (Catalog # 1224-PL; 10 µg/mL) or B7-H3 (4Ig)/B7-H3b (Catalog # 2318-B3; 10 µg/mL).