Epigallocatechin gallate, the main polyphenol in green tea, binds to the T-cell receptor, CD4: Potential for HIV-1 therapy - 20/08/11
, William T. Shearer, MD, PhD b
Reprint requests: Christina L. Nance, PhD, Department of Allergy and Immunology, Texas Children’s Hospital, 6621 Fannin, MC: FC330.01, Houston, TX 77030.Sheffield, United Kingdom, and Houston, Tex
Abstract |
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 Kd 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.
Le texte complet de cet article est disponible en PDF.Key words : HIV-1, gp120, CD4, EGCG, NMR, STD, flow cytometry
Abbreviations used : EGCG, FITC, Gp, NMR, STD
Plan
| Supported by National Institutes of Health grants AI27551, AI36211, HD41983, RR0188, HL079533, HL72705, and RAT003084A and contract AI41089; the Pediatric Research and Education Fund, Baylor College of Medicine; and the David Fund, Pediatrics AIDS Fund, and Immunology Research Fund, Texas Children’s Hospital. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 118 - N° 6
P. 1369-1374 - décembre 2006 Retour au numéro
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