CYTOTOXIC T-LYMPHOCYTE RESPONSES TO MEASLES IN W AFRICA

该项目广泛的长期目标是获得免疫知识 西非人细胞毒性T淋巴细胞(CTL)对麻疹的影响 麻疹的感染麻疹或接种麻疹疫苗的《公约》的具体目标 项目有：(1)检测CD8+CTL是否发生直接杀伤 并确定3种麻疹抗原中的哪一种， 血凝素(HA)、融合蛋白(F)或核蛋白(NP)，这 免疫的类型是直接的。为了实现这一目标，重组 表达这些蛋白的牛痘/麻疹病毒将被用来感染 供者与HLA类L基因座匹配的B细胞靶点检测 细胞毒性试验。(2)检测重组疫苗是否具有减毒作用 牛痘/麻疹病毒和金丝雀痘/麻疹重组病毒，它们是 未来麻疹疫苗的候选者，可用于召回CTL 最近感染麻疹的儿童和儿童 接种了麻疹疫苗。为了实现这一目标，这些不可复制的 病毒载体将被用来感染自体单个核细胞 刺激CTL杀伤感染麻疹的自体B细胞靶点 病毒。使用抗CD4和抗CD8抗体将定义哪种类型的 细胞效应杀戮。(3)使用1和2中描述的方法进行测试， 暴露于天然麻疹是否增强免疫母亲的CTL反应 对麻疹和接种麻疹疫苗的兄弟姐妹来说。(4)识别 猪传染性支气管炎病毒HA、F和NP抗原的多肽表位 埃德蒙斯顿和当地的麻疹病毒株，它们是由人类白细胞抗原识别的 1类西非人常见的受限CTL。氨基酸序列 将对3种麻疹抗原中的哪一种进行检测，以预测哪种会与之结合 常见的西非人类白细胞抗原1类基序，然后将在 用转导这些基因的T2突变细胞进行组装实验。 那些具有高亲和力的结合将在细胞毒性测试中进行测试。 从上述研究中获得的知识将使我们能够决定是否 减毒的麻疹重组病毒很可能有用 西非的疫苗。

The broad long term aim of this Project is to gain knowledge of immunity to measles effected by cytotoxic T lymphocytes (CTL) in West Africans infected with, or vaccinated against, measles. The specific aims of the project are: (1) to test whether direct killing by CD8 + CTL occurs in the acute phase of measles and to determine to which of 3 measles antigens, the hemagglutinin (HA), the fusion (F) or the nucleoprotein (NP), this type of immunity is directed. To achieve this aim recombinant vaccinia/measles viruses expressing these proteins will be used to infect B cell targets matched by HLA class l locus of the donor and tested in cytotoxicity assays. (2) to test whether recombinant attenuated vaccinia/measles viruses and canary pox/measles recombinants, which are candidates for future measles vaccines, can be used to recall CTL in children who have recently been infected with measles and in children vaccinated against measles. To achieve this aim, these non-replicating virus vectors will be used to infect autologous mononuclear cells in order to stimulate CTL to kill autologous B cell targets infected with measles virus. Use of anti CD4 and anti CD8 antibody will define which type of cell effects killing. (3) to test, using methods described in 1 and 2, whether exposure to natural measles boosts CTL responses in mothers immune to measles and in siblings vaccinated against measles. (4) to identify the peptide epitopes contained in the HA, F and NP antigens of the Edmonston and local strains of measles virus, which are recognized by HLA class 1 restricted CTL common to West Africans. The amino acid sequences of the 3 measles antigens will be examined to predict which will bind to the common West African HLA class 1 motifs and will then be tested in assembly assays using T2 mutant cells transfected with these HLA genes. Those that bind with high affinity will be tested in cytotoxicity assays. Knowledge gained from the above studies will allow decisions as to whether the attenuated measles recombinant viruses are likely to be useful vaccines in West Africa.