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-IgG₂ (PRO 542®). 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 μmol/L CD4 to 310 μmol/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 μmol/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.

Key words: HIV-1, gp120, CD4, EGCG, NMR, STD, flow cytometry

Abbreviations used: EGCG, Epigallocatechin gallate, FITC, Fluorescein isothiocyanate, Gp, Glycoprotein, NMR, Nuclear magnetic resonance, STD, Saturation transfer difference