title: Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein.
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.
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Bryony
authors.initials: B
authors.lastname: Jenkins
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: Urszula
authors.initials: U
authors.lastname: Eksmond
authors.affiliation: The Francis Crick Institute, London, UK.
authors.forename: George
authors.initials: G
authors.lastname: Young
authors.affiliation: The Francis Crick Institute, London, UK.|Department of Medicine, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: George
authors.identifier: 0000-0002-8457-2633
authors.initials: G
authors.lastname: Kassiotis
keywords: Immunosuppressive domain; T cell receptor; T cell response; peptide-MHC II complex; retroviral envelope