Identification of the HLA-A24 Peptide Epitope within Cytomegalovirus Protein pp65 Recognized by CMV-Specific Cytotoxic T Lymphocytes

Abstract

Among cytomegalovirus (CMV) tegument proteins, phosphoprotein 65 (pp65) has been identified as the important target antigen of the cytotoxic T lymphocyte (CTL) response against the virus. We synthesized seven CMV-pp65-derived peptides carrying an HLA-A24-binding motif, and investigated the ability of these peptides to induce CMV-specific CTL. We identified one nonamer peptide (pp65113-121; VYALPLKML) able to bind HLA-A24 and induce CTL responses in vitro in peripheral blood mononuclear cells (PBMC) from CMV-seropositive individuals. The peptide-specific CTLs generated were capable of recognizing pp65 expressed on CMV-infected fibroblasts as well as pp65113-121 peptide bound to the surface of C1R-A*2402 cells in an HLA-A24-restricted manner. The pp65113-121 peptide thus might be considered a synthetic peptide vaccine in HLA-A24-positive individuals.

Evaluation of cytomegalovirus-specific cytotoxic T-lymphocytes in patients with the HLA-A*02 or HLA-A*24 phenotype undergoing hematopoietic stem cell transplantation

“…These facts suggest the presence of a potent CMV epitope that is restricted to HLA-A*24. The contributions of other HLA-A*24 epitopes, such as VYALPLKML (VYA), 13,16,22 AYAQKIFKIL (AYA) 23 and FTSQYRIQGKL (FTS), 10 have been reported, but tetramer-based analysis has only been performed in A*24QYD. 5 Furthermore, it has been reported that IFN-g secretion after stimulation with VYA was significantly lower than that with A*24QYD, 16 which does not have the capacity to sensitize T cells even at a higher concentration of 10 mM.…”

Recognition of cmv pp65 protein antigen by human cd4 t-cell lines induced with an immunodominant peptide pool

“…Five CD4 peptides have been defined on pp65 in contrast to the numerous CD8 peptides [12,15,21,30,[33][34][35][36][37][38]. Most of the reports also tried to optimized culture condition for CD8 cells.…”

The impact of HLA‐B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV

“…Large numbers of these CD8 + T cells are maintained in healthy virus carriers, with focussed specificity towards a number of viral antigens including the immediate-early 1 antigen and the structural phosphoproteins pp50, pp65 and pp150 [4,5]. The CTL response to pp65 is one of the strongest antigenspecific responses identified in healthy individuals [6][7][8] and is therefore ideal for investigations into the controlling influences over the immune response to persistent antigens.…”