Fig. 4.

Peptide mimetics of the B7-2 homodimer interface are superantigen antagonists. (A) In the CTLA-4/B7-2 complex (1I85.pdb) (1), B7-2 is shown in gray and CTLA-4 in blue, with homodimer interface domains of CTLA-4 in red (YVIDPE) and green (VVLASS) and its B7 binding site (MYPPPY) in yellow. Residues in the crystallographic B7-2 homodimer interface (1) are shown in magenta and pink; those in magenta are represented in mimetic peptides. (B) Peptide mimetics of the B7-2 dimer interface. In the extracellular domain of B7-2, residues in the dimer interface are underlined in cyan; residues that contact CTLA-4 are in boldface. Peptide sequences are marked with colors; in pB2-7, blue-gray residues overlap with pB2-4 and pB2-6, respectively. (C) Location of peptides from B in the B7-2 structure (1I85.pdb), in corresponding colors. (D) Peptides pB2-4 (EKFDSVHSKYM) and pB2-6 (DSDSWTLR) antagonize induction of IFN-γ by SEB. PBMCs were induced with SEB (10 ng/mL), in the absence (open circles) or presence (filled circles) of 0.1 μg/mL peptide as shown. Secreted IFN-γ was determined (pg/mL ×10⁻²). (E) Synergy between pB2-4 and pB2-6. PBMCs were induced with SEB (0.1 ng/mL), in the absence or presence of 0.01 μg/mL pB2-4, pB2-6, or both. Secreted IL-2, IFN-γ, TNF-α, and IL-10 were determined. (F) Superantigen antagonist activity of B7-2 dimer interface mimetic peptide pB2-7. PBMCs were induced with SEB (0.1 ng/mL) alone or together with 0.1 μg/mL of pB2-7 (MGRTSFDSDS) or 0.01 μg/mL of each pB2-4 and pB2-6. Secreted IL-2, IFN-γ, TNF-α, and IL-10 were determined.