Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy

Background: The green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells. Objective: To demonstrate that EGCG binds to the CD4 molecule at the gp120 attachment site and inhibits gp120 binding at physiologically relevant levels, thus establishing EGCG as a potential therapeutic treatment for HIV-1 infection. Methods: Nuclear magnetic resonance spectroscopy was used to examine the binding of EGCG and control, (-)-catechin, to CD4-IgG(2) (PRO 542 (R)). Gp120 binding to human CD4(+) T cells was analyzed by flow cytometry. Results: Addition of CD4 to EGCG produced a linear decrease in nuclear magnetic resonance signal intensity from EGCG but not from the control, (-)-catechin. In saturation transfer difference experiments, addition of 5.8 mu mol/L CD4 to 310 mu mol/L EGCG produced strong saturation at the aromatic rings of EGCG, but identical concentrations of (-)-catechin produced much smaller effects, implying EGCG/CD4 binding strong enough to reduce gp120/CD4 binding substantially. Molecular modeling studies suggested a binding site for EGCG in the D1 domain of CD4, the pocket that binds gp120. Physiologically relevant concentrations of EGCG (0.2 mu mol/L) inhibited binding of gp120 to isolated human CD4(+) T cells. Conclusion: We have demonstrated clear evidence of high-affinity binding of EGCG to the CD4 molecule with a K-d of approximately 10 nmol/L and inhibition of gp120 binding to human CD4(+) T cells. Clinical implications: Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.