HIV-1 gp41 and TCRα Trans-Membrane Domains Share a Motif Exploited by the HIV Virus to Modulate T-Cell Proliferation

Tomer Cohen,Shmuel Jaffe Cohen,Irun R Cohen,Niv Antonovsky,Yechiel Shai

doi:10.1371/journal.ppat.1001085

Tomer Cohen, Shmuel Jaffe Cohen + Show 3 more

Open Access

https://doi.org/10.1371/journal.ppat.1001085

Copy DOI

Journal: PLoS Pathogens	Publication Date: Sep 2, 2010
Citations: 80	License type: CC BY 4.0

Affiliation: Weizmann Institute of Science

Abstract

Viruses have evolved several strategies to modify cellular processes and evade the immune response in order to successfully infect, replicate, and persist in the host. By utilizing in-silico testing of a transmembrane sequence library derived from virus protein sequences, we have pin-pointed a nine amino-acid motif shared by a group of different viruses; this motif resembles the transmembrane domain of the α-subunit of the T-cell receptor (TCRα). The most striking similarity was found within the immunodeficiency virus (SIV and HIV) glycoprotein 41 TMD (gp41 TMD). Previous studies have shown that stable interactions between TCRα and CD3 are localized to this nine amino acid motif within TCRα, and a peptide derived from it (TCRα TMD, GLRILLLKV) interfered and intervened in the TCR function when added exogenously. We now report that the gp41 TMD peptide co-localizes with CD3 within the TCR complex and inhibits T cell proliferation in vitro. However, the inhibitory mechanism of gp41 TMD differs from that of the TCRα TMD and also from the other two known immunosuppressive regions within gp41.

Highlights

The transmembrane domains (TMDs) of the T-cell receptor (TCR) play an important role in the assembly of the receptor complex
TCR TMDs play an important role in the assembly of the receptor complex composed of the TCR subunits and the CD3 co-receptor chains
We show that a synthetic peptide derived from gp41 TMD co-localizes with CD3 and inhibits T-cell proliferation in vitro

Summary

Introduction

The transmembrane domains (TMDs) of the T-cell receptor (TCR) play an important role in the assembly of the receptor complex. It has been shown that one basic and two acidic transmembrane residues, within these nine residues, are required for the assembly of each of the three CD3 signaling dimmers (d-e, c-e, f-f) with the TCR [4]. In concert with the latter, Manolios et al have shown that the stable interactions between the TCRa and CD3 are localized to a short region within the transmembrane domain of TCRa. In concert with the latter, Manolios et al have shown that the stable interactions between the TCRa and CD3 are localized to a short region within the transmembrane domain of TCRa They have shown that the charged amino acids arginine and lysine are essential for this interaction [5,6,7]. A nine aminoacid peptide derived from the TCRa transmembrane domain, which includes these two charged amino acids (TCRa TMD, GLRILLLKV), interfered and intervened in the TCR function when added exogenously [8]

Methods

Results

Discussion

Conclusion