Wyckoff J H, Osmand A P, Eisenberg R J, Cohen G H, Rouse B T
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville.
Immunobiology. 1988 May;177(2):134-48. doi: 10.1016/S0171-2985(88)80034-2.
Four synthetic peptides which correspond to continuous antibody epitopes of herpes simplex virus (HSV) type 1 glycoprotein D (gD) within amino acid residues 1-23 (8-23), 268-287 and 340-356 were evaluated for in vitro stimulating activity on HSV-primed murine T lymphocytes. All peptides stimulated lymphoproliferative responses and interleukin 2 (IL2) production from draining lymph node (LN) cell populations taken 5 days after footpad immunization with live HSV. Similar responses were elicited from splenic memory T cells only if these T cells were restimulated with HSV in vitro and rested prior to peptide stimulation. Furthermore, peptide stimulated memory T cell populations released soluble factor(s) into the culture supernates which modulated the induced lymphoproliferative and cytotoxic T lymphocyte (CTL) activities of HSV-stimulated, HSV-immune splenocytes (indicator cultures). Memory T cell supernates suppressed lymphoproliferation of indicator cultures, while CTL activity of indicator cultures was either enhanced or suppressed, depending on the peptide and concentration. In contrast, supernates generated by peptide stimulation of draining LN cells had no effect on CTL activity of indicator cultures. However, the lymphoproliferative responses were augmented with three of the four peptides at the highest concentration of peptides tested. Our experiments indicate T helper (Th) and T suppressor (Ts) lymphocyte recognition of four synthetic peptides which encompass continuous antibody epitopes of HSV gD. Immunization with one of these peptides (1-23) induces virus neutralizing antibodies and protection against lethal viral challenge. Th lymphocyte recognition of this peptide in particular, together with its observed function in the induction of protection against HSV infection, indicates that this peptide is a promising candidate as a synthetic vaccine against HSV infection.
对四种合成肽进行了评估，它们分别对应单纯疱疹病毒1型糖蛋白D（gD）氨基酸残基1 - 23（8 - 23）、268 - 287和340 - 356内的连续抗体表位，以检测其对经HSV致敏的小鼠T淋巴细胞的体外刺激活性。在用活HSV进行足垫免疫5天后采集的引流淋巴结（LN）细胞群体中，所有肽均刺激了淋巴细胞增殖反应和白细胞介素2（IL2）的产生。只有当脾记忆T细胞在体外先用HSV再刺激并在肽刺激前进行休整后，才能从这些T细胞中引发类似反应。此外，肽刺激的记忆T细胞群体向培养上清液中释放了可溶性因子，这些因子调节了HSV刺激的、HSV免疫脾细胞（指示培养物）诱导的淋巴细胞增殖和细胞毒性T淋巴细胞（CTL）活性。记忆T细胞上清液抑制了指示培养物的淋巴细胞增殖，而指示培养物的CTL活性则根据肽和浓度的不同而增强或受到抑制。相比之下，肽刺激引流LN细胞产生的上清液对指示培养物的CTL活性没有影响。然而，在测试的最高肽浓度下，四种肽中的三种增强了淋巴细胞增殖反应。我们的实验表明，辅助性T（Th）淋巴细胞和抑制性T（Ts）淋巴细胞识别包含HSV gD连续抗体表位的四种合成肽。用其中一种肽（1 - 23）免疫可诱导病毒中和抗体并提供针对致死性病毒攻击的保护。特别是Th淋巴细胞对该肽的识别，以及其在诱导抗HSV感染保护中的观察到的功能，表明该肽作为抗HSV感染的合成疫苗是一个有前景的候选物。
