Identification of novel immunodominant CD4+ Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity
Identification of novel immunodominant CD4+ Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity
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DOI：
10.1128/jvi.77.17.9463-9473.2003
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Nesburn, AB
中科院分区：
文献类型：
--
作者：
BenMohamed, L;Bertrand, G;Nesburn, AB
单纯疱疹病毒（HSV）抗原表位库的分子特征将极大地扩展我们对单纯疱疹病毒免疫的认识，并改善对疱疹病毒感染的免疫干预。HSV糖蛋白D （gD）是一种具有免疫优势的病毒外壳蛋白，被认为是一种很好的疫苗候选抗原。通过使用TEPITOPE预测算法，我们在HSV-1型（HSV-1）携带gD的潜在CD4(+) t细胞表位中鉴定并表征了总共12个区域，每个区域的长度为27至34个氨基酸。相应的中等大小肽的免疫原性研究证实了所有已知的gD表位，并发现了四个新的免疫优势区(gD(49-82), gD(146-179), gD（228-257）和gD(332-358))，每个都含有天然加工的表位。这些表位在不同主要组织相容性复合物背景的小鼠中引起了有效的t细胞反应。四个新的免疫优势肽表位中的每一个都产生强大的CD4(+) Th1 T细胞，这些细胞对hsv -1感染的骨髓来源的树突状细胞具有生物活性。重要的是，用四个新发现的CD4(+) Th1肽表位而不是CD4(+) Th2肽表位免疫H-2(d)小鼠，诱导了对致命的眼部HSV-1攻击的强大保护性免疫。这些肽表位可能被证明是有效的疱疹免疫预防策略的重要组成部分。
The molecular characterization of the epitope repertoire on herpes simplex virus (HSV) antigens would greatly expand our knowledge of HSV immunity and improve immune interventions against herpesvirus infections. HSV glycoprotein D (gD) is an immunodominant viral coat protein and is considered an excellent vaccine candidate antigen. By using the TEPITOPE prediction algorithm, we have identified and characterized a total of 12 regions within the HSV type 1 (HSV-1) gD bearing potential CD4(+) T-cell epitopes, each 27 to 34 amino acids in length. Immunogenicity studies of the corresponding medium-sized peptides confirmed all previously known gD epitopes and additionally revealed four new immunodominant regions (gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), each containing naturally processed epitopes. These epitopes elicited potent T-cell responses in mice of diverse major histocompatibility complex backgrounds. Each of the four new immunodominant peptide epitopes generated strong CD4(+) Th1 T cells that were biologically active against HSV-1-infected bone marrow-derived dendritic cells. Importantly, immunization of H-2(d) mice with the four newly identified CD4(+) Th1 peptide epitopes but not with four CD4(+) Th2 peptide epitopes induced a robust protective immunity against lethal ocular HSV-1 challenge. These peptide epitopes may prove to be important components of an effective immunoprophylactic strategy against herpes.