Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein

Bryony Jenkins,George Young,George Kassiotis,Urszula Eksmond

doi:10.12688/wellcomeopenres.10269.1

Abstract

To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs) of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II), and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

Highlights

Using three T cell receptors (TCRs) of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides
These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity
The following sentence in the last paragraph of Results and Discussion: “In contrast, neither peptide fusion affected the response of the DO11.10 clone (Figure 2B), indicating that effects of the immunosuppressive peptides can be observed in some TCRpMHC pairs, but not others.”

Summary

Introduction

Several studies over the last three decades have provided evidence to suggest that the envelope glycoprotein of certain retroviruses is immunosuppressive in vitro and in vivo (Cianciolo et al, 1985; de Parseval et al, 2001; Denner, 2014; Dupressoir et al, 2012; Haraguchi et al, 1997; Kudo-Saito et al, 2014; Mangeney et al, 2007; Schlecht-Louf et al, 2010). Synthetic peptides corresponding to a region of 17-amino acid residues from the murine leukemia virus (MLV) envelope glycoprotein inhibit immune function in a variety of assays. These assays measure distinct aspects of immune responsiveness. Others measure antigen-specific T and B cell responses to immunization with synthetic peptides, recombinant envelope domains, and to infection with MLVs (Morozov et al, 2012; Schlecht-Louf et al, 2014; Schlecht-Louf et al, 2010). We examine the properties of T cell epitopes linked to the immunosuppressive domain and provide an alternative interpretation for the effects

Methods

Results

Conclusion