A CTL epitope from human cytomegalovirus IE1 defined by combining prediction of HLA binding and proteasomal processing is the target of dominant immune responses in patients after allogeneic stem cell transplantation

: Objectives and methodsIn an attempt to define HCMV IE1-derived, HLA-A&ast;0201-restricted epitopes, an advanced computer-based epitope prediction combining HLA binding and proteasomal cleavages in silico was performed.: ResultsThis prediction algorithm clearly confirmed VLEETSVML to be the most likely CTL epitope. By tetramer staining, HCMV pp65 NLVPMVATV-specific CD8+ T cells were detectable in 18/24 HCMV seropositive HLA-A&ast;0201-expressing individuals (median frequency 0.58%; range 0.1%–4.7%), and IE1 VLEETSVML-specific CD8+ T cells in 5/24 (median frequency 2.1%; range 0.1%–4.3%), respectively (p<0.01). Also in recipients of an allogeneic SCT, VLEETSVML- and NLVPMVATV-specific CD8+ T cells were detectable in comparable frequencies, but again the number of patients with detectable pp65-specific CD8+ T cells was higher (p = 0.014). In 4/15 individuals, all demonstrating IE1 VLEETSVML-specific CD8+ T cells prior to peptide stimulation, VLEETSVML-specific T cell lines (purity of 42.6%–98.6% of all CD3+/CD8+ T cells) were successfully generated after 2–4 weeks of culture using the IFN-γ secretion assay.: ConclusionIn conclusion, this novel prediction strategy efficiently predicted an immunodominant viral T-cell epitope. [Copyright &y& Elsevier]