Identification of CD8+ T cell epitopes in the immediate early 62 protein (IE62) of varicella-zoster virus, and evaluation of frequency of CD8+ T cell response to IE62, by use of IE62 peptides after varicella vaccination.
Varicella-zoster virus (VZV) causes varicella, establishes neuronal latency, and can reactivate, resulting in herpes zoster. VZV-specific T cells are important for controlling infection. VZV immediate early protein 62 (IE62) is recognized by cytotoxic T cells from immune individuals, but no CD8(+) T cell epitopes have been defined for any VZV protein. CD8(+) T cell frequencies were assessed by cytokine flow cytometry (CFC), by use of synthetic-peptide pools corresponding to the IE62 sequence. IE62 peptide-specific CD8(+) T cells were below the threshold of detection, by direct CFC of either whole blood or peripheral blood mononuclear cells (PBMCs). Activated CD8(+)CD69(+) T cells that produced interferon-gamma were detectable after in vitro restimulation of PBMCs, and restricted epitopes were identified for HLA-A*0201-positive subjects. Varicella vaccination of 3 VZV-immune subjects was associated with increases in IE62 peptide-specific CD8(+) T cells, a finding indicating that in vivo re-exposure boosts memory immunity to this important viral protein.
Frey
Christian R
CR
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA, and Faculty of Biosciences, University of Witten/Herdecke, Witten, Germany.
Sharp
Margaret A
MA
Min
Andrew S
AS
Schmid
D Scott
DS
Loparev
Vladimir
V
Arvin
Ann M
AM
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002644:Chickenpox / Q000276:immunology; D019433:Chickenpox Vaccine / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015534:Trans-Activators / Q000276:immunology*; D014611:Vaccination; D014759:Viral Envelope Proteins / Q000276:immunology*
D019433:Chickenpox Vaccine; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins