Bergen R E, Sharp M, Sanchez A, Judd A K, Arvin A M
Department of Pediatrics, Stanford University School of Medicine, California.
Viral Immunol. 1991 Fall;4(3):151-66. doi: 10.1089/vim.1991.4.151.
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) greater than or equal to 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.
在大多数健康受试者中，水痘带状疱疹病毒（VZV）感染可引发针对即刻早期（IE62）蛋白和糖蛋白I（gp I）的持续性细胞介导免疫。在这些实验中，对应于IE62蛋白和gp I残基的合成肽被用于鉴定这些免疫原性VZV蛋白的线性氨基酸序列，这些序列可被已知主要组织相容性复合体（MHC）类型的VZV免疫个体的外周血T淋巴细胞识别。12名VZV免疫供者对10种合成IE62肽中的至少两种均有T细胞增殖反应，即刺激指数（SI）大于或等于2.0；VZV免疫供者的T细胞识别的IE62肽的平均数量为7种。10种IE62肽中的5种刺激了75%至83%的VZV免疫供者的T细胞；其他5种IE62肽被42%至67%的受试者的T细胞识别。所有VZV免疫供者对10种合成gp I肽中的至少两种也有T增殖反应；识别的肽的平均数量为6种。10种gp I肽中的6种被67%至92%的VZV免疫供者的T细胞识别；对其他gp I肽有反应的供者频率为42%至58%。5名非免疫供者对任何IE62或gp I肽均未表现出T细胞增殖。两种IE62肽的组合提供了可被所有12名VZV免疫供者的T细胞识别的表位，无论其DR类型如何。同样，一种gp I肽与另外两种gp I肽中的任何一种组合均可诱导所有免疫受试者的T细胞增殖。在20多年前曾患原发性VZV感染的受试者中检测到了对IE62蛋白和gp I的多个短氨基酸序列具有特异性的记忆T细胞。这些观察结果表明，自然VZV感染可引发对病毒蛋白的多种细胞介导免疫反应，并不局限于一两个免疫显性区域。尽管肽疫苗的有效性仍有待确定，但已鉴定出IE62蛋白和gp I的多个表位，这些表位可由抗原呈递细胞（APC）呈递，并被“杂种”人群中大多数受试者的T细胞识别。
