Phenotypic analysis of human CD4+ T cells specific for immediate-early 63 protein of varicella-zoster virus.
Open reading frame 63 of varicella-zoster Virus (VZV) encodes an immediate early (IE) phosphoprotein (IE63) that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication; however, data addressing the existence of IE63 protein-specific CD4+ T cells are limited. Using IFN-gamma immunosorbent assays, we identified high frequencies of responses to overlapping peptides spanning the IE63 protein both ex vivo and after in vitro restimulation in healthy VZV-seropositive individuals. We identified a commonly recognised epitope, restricted by HLA-DRB1*1501, which was naturally processed and presented by keratinocytes. We proceeded to investigate the frequency and phenotype of the epitope-specific CD4+ T cells using HLA class II tetrameric complexes. Epitope-specific CD4+ T cells were detectable ex vivo and showed a mixed central and effector-memory differentiation phenotype, with a significant proportion showing evidence of recent activation and rapid effector function. In summary these data implicate persistent low-level or recurrent VZV antigen exposure in healthy immune donors and are compatible with a role for IE63-specific CD4+ T cells in the control of viral reactivation.
Jones
Louise
L
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, and Department of Dermatology, Churchill Hospital, Oxford, UK. louise.jones@imm.ox.ac.uk
Black
Antony P
AP
Malavige
Gathsaurie N
GN
Ogg
Graham S
GS
D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D014645:Herpesvirus 3, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007156:Immunologic Memory; D016130:Immunophenotyping; D015603:Keratinocytes / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014775:Virus Activation
D000956:Antigens, Viral; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D017874:Immediate-Early Proteins; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C074551:immediate early protein 63, Human herpesvirus 3