HIV-1 GENE PRODUCTS TARGETED TO MHC II ANTIGEN PRESENTAT

描述：(摘自摘要)。拟议研究的重点 是将HIV-1基因产物定位于主要组织相容性II类(MHC) 二)抗原加工和提呈的途径。为了实现这一目标， 研究人员开发了一系列新的编码基因结构 HIV嵌合抗原与溶酶体膜靶向序列的融合 糖蛋白(LAMP)。在初步研究中，调查人员已经表明 HIV包膜蛋白与LAMP胞质尾部序列融合 表现出增强的免疫反应，这归因于 通过抗原提呈将MHC II肽提呈给CD4+T细胞 细胞。调查员提出了三个具体目标： 具体目标1：针对HIV-1 env、Gag、Polo的LAMP靶向技术的应用 和nef抗原结合到MHC II途径，从而增加CD4+辅助T细胞 对这些病毒的免疫反应随之增强 抗原。 特定目标2：强调细胞质/核的CTL反应 蛋白质作为促进对保守病毒的细胞溶解反应的手段 HIV-1感染细胞中的蛋白质。 具体目标3：适用在调查员的 LAMP联合靶向DNA促进基因转移的研究机构 当注射质粒DNA时抗原提呈细胞的数量 肌肉内。 研究人员指出，将构建SIV-LAMP嵌合体 利用适合于非人类免疫的重组痘苗病毒载体 并用于分析灵长类动物的保护性免疫 SIV型号。

DESCRIPTION: (Taken from the abstract). The focus of the proposed research is to target HIV-1 gene products to major histocompatibility class II (MHC II) pathways for antigen processing and presentation. Towards this goal, the investigator has developed a novel series of gene constructs encoding chimeric HIV antigens fused to the targeting sequence of lysosomal membrane glycoproteins (LAMP). In preliminary studies, the investigator has shown that HIV envelope protein fused with the LAMP cytoplasmic tail sequence exhibited an enhanced immune response which is attributed to increase in the MHC II peptide concentration presented to CD4+ T cells by antigen presenting cells. The investigator proposes three specific aims: Specific Aim 1: The application of LAMP-targeting of HIV-1 env, gag, pol and nef antigens to MHC II pathway so as to increase the CD4+ helper T cell response with a consequent increase in the immune response to these antigens. Specific Aim 2: An emphasis on the CTL response of cytoplasmic/nuclear proteins as a means to promote cytolytic response against conserved viral proteins in HIV-1 infected cells. Specific Aim 3: To apply procedures developed at the investigator's institution for conjunction of LAMP targeting DNAs to promote transfection of antigen presenting cells when the plasmid DNA is injected intramuscularly. The investigator points out that the SIV-LAMP chimeras will be constructed using a recombinant vaccinia vector suitable for immunization of non-human primates and made available for analysis of protective immunization in the SIV models.