Cross-reactive recognition of human and primate cytomegalovirus sequences by human CD4 cytotoxic T lymphocytes specific for glycoprotein B and H.
Although the importance of CD4+ T cell responses to human cytomegalovirus (HCMV) has recently been recognized in transplant and immunosuppressed patients, the precise specificity and nature of this response has remained largely unresolved. In the present study we have isolated CD4+ CTL which recognize epitopes from HCMV glycoproteins gB and gH in association with two different HLA-DR antigens, DRA1*0101/DRB1*0701 (DR7) and DRA1*0101/DRB1*1101 (DR11). Comparison of amino acid sequences of HCMV isolates revealed that the gB and gH epitope sequences recognized by human CD4+ T cells were not only conserved in clinical isolates from HCMV but also in CMV isolates from higher primates (chimpanzee, rhesus and baboon). Interestingly, these epitope sequences from chimpanzee, rhesus and baboon CMV are efficiently recognized by human CD4+ CTL. More importantly, we show that gB-specific T cells from humans can also efficiently lyse peptide-sensitized Patr-DR7+ cells from chimpanzees. These findings suggest that conserved gB and gH epitopes should be considered while designing a prophylactic vaccine against HCMV. In addition, they also provide a functional basis for the conservation of MHC class II lineages between humans and Old World primates and open the possibility for the use of such primate models in vaccine development against HCMV.
Elkington
Rebecca
R
Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia.
Shoukry
Naglaa H
NH
Walker
Susan
S
Crough
Tania
T
Fazou
Chrysa
C
Kaur
Amitinder
A
Walker
Christopher M
CM
Khanna
Rajiv
R
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010215:Papio; D010446:Peptide Fragments / Q000276:immunology; D010449:Peptide Mapping; D014759:Viral Envelope Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; D007371:Interferon-gamma