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*
Anthony Nolan Research Institute and
Department of Immunology, The Royal Free and University College Medical School, London, United Kingdom;
Department of Cardiological Sciences, British Heart Foundation Cardiovascular Pathology Unit, St. George’s Hospital Medical School, London, United Kingdom; and
§
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
The Ag specificity of the CTL response against CMV is directed
almost entirely to a single CMV tegument protein, the phosphoprotein
pp65. We report the identification of three peptides derived from the
protein pp65 that displayed a high or intermediate binding to
HLA-A*0201 molecules, which were also able to induce an in vitro CTL
response in peripheral blood lymphocytes from CMV seropositive
individuals. The peptide-specific CTLs generated were capable of
recognizing the naturally processed pp65 either presented by
CMV-infected cells or by cells infected with an adenovirus construct
expressing pp65 in an HLA-A*0201-restricted manner. Thus, we were able
to demonstrate responses to subdominant CTL epitopes in CMV-pp65 that
were not detected in polyclonal cultures obtained by conventional
stimulations. We also found that the amino acid sequences of the three
peptides identified as HLA-A*0201-restricted CTL epitopes were
conserved among different wild-type strains of CMV obtained from renal
transplant patients, an AIDS patient, and a congenitally infected
infant, as well as three laboratory strains of the virus (AD169, Towne
and Davis). These observations suggest that these pp65 CTL peptide
epitopes could potentially be used as synthetic peptide vaccines or for
other therapeutic strategies aimed at HLA-A*0201-positive individuals,
who represent 
40% of the European Caucasoid population. However,
strain variation must be taken in consideration when the search for CTL
epitopes is extended to other HLA class I alleles, because these
mutations may span potential CTL epitopes for other HLA molecules, as
it is described in this study.
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