Human T Cells Recognize Multiple Epitopes of an Immediate Early/Tegument Protein (IE62) and Glycoprotein I of Varicella Zoster Virus

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Abstract
Infection with varicella zoster virus (VZV) elicits persistent cell-mediated immunity directed against the immediate early (IE62) protein and the glycoprotein I (gp I) in most healthy subjects. In these experiments, synthetic peptides corresponding to residues of the IE62 protein and gp I were used to identify linear amino acid sequences of these immunogenic VZV proteins that were recognized by peripheral blood T lymphocytes from VZV-immune individuals of known major histocompatibility complex (MHC) type. All of 12 VZV-immune donors had T-cell proliferative responses, defined as a stimulation index (SI) ≥ 2.0, to at least two of ten synthetic IE62 peptides; the mean number of IE62 peptides recognized by T cells from VZV-immune donors was seven. Five of the ten IE62 peptides stimulated T cells from 75% to 83% of the VZV-immune donors; the other five IE62 peptides were recognized by T cells from 42% to 67% of the subjects. All VZV-immune donors also had T proliferation responses to at least two of ten synthetic gp I peptides; the mean number of peptides recognized was six. Six of the ten gp I peptides were recognized by T cells from 67% to 92% of the VZV-immune donors; the frequency of donors responding to the other gp I peptides ranged from 42% to 58%. None of five nonimmune donors demonstrated T-cell proliferation to any of the IE62 or gp I peptides. A combination of two IE62 peptides provided epitopes that could be recognized by T cells from all twelve VZV-immune donors, regardless of DR type. Similarly, one gp I peptide in combination with either of two other gp I peptides induced proliferation of T cells from all immune subjects. Memory T cells with specificity for multiple short amino acid sequences of the IE62 protein and gp I were detected in subjects who had had primary VZV infection more than 20 years earlier. These observations indicate that natural VZV infection elicits a diverse cell-mediated immune response to viral proteins that is not restricted to only one or two immunodominant regions. Although the usefulness of peptide vaccines remains to be established, multiple epitopes of the IE62 protein and gp I were identified that could be presented by antigen-presenting cells (APC) and recognized by T cells from most subjects in an "outbred" human population.

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