Identification of a conserved HLA-A2-restricted decapeptide from the IE1 protein (pUL123) of human cytomegalovirus.
Control of human cytomegalovirus (HCMV) infection is predominantly mediated by cytolytic CD8+ T lymphocytes (CTL). Among the roughly 200 HCMV-encoded polypeptides, the tegument protein pp65 (ppUL83) and the nonstructural IE1 protein are considered to be dominant CTL targets. Yet the importance of CTL against IE1 for protective immunity against HCMV reactivation and disease has remained elusive. Analyses have been difficult, as all MHC class I presented peptides of IE1 defined so far are located in parts of the protein that are variable between viral strains. In this study a conserved decameric peptide from IE1 (P6, IE1(354-363)) that bound to HLA-A2 was identified. Using peptide-pulsed, HLA-matched stimulator cells, CTL lines which recognized P6 after exogenous loading as well as after endogenous processing could repeatedly be generated. However, memory CTL directed against P6 were not readily detectable by ex vivo ELISPOT analysis in peripheral blood mononuclear cells of healthy seropositive individuals, indicating that this peptide represents a quantitatively subdominant determinant during latent HCMV infection. Using the conserved HLA-A2 presented peptide P6 will enable more detailed studies on the role of IE1-specific CTL in patients suffering from various HCMV-related disease conditions and investigation of the role of such cells for immune control of HCMV. Since IE1 is the first viral protein to be expressed after reactivation from latency, P6 may also serve as an important component of a future recombinant HCMV vaccine.
Frankenberg
Nadine
N
Institut für Virologie, Johannes Gutenberg-Universität Mainz, Obere Zahlbacher Strasse 67, 55131, Mainz, Germany.
Pepperl-Klindworth
Sandra
S
Meyer
Ralf G
RG
Plachter
Bodo
B
D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins; D017735:Virus Latency
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010446:Peptide Fragments; D010455:Peptides; D014764:Viral Proteins; C459402:peptide IE1 (354-363)