HIV-1-ASSOCIATED SUPERANTIGEN

HIV-1相关超抗原

• 批准号: 2068316
• 负责人: DAVID N POSNETT
• 金额: $ 28.31万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2068316
• 关键词: AIDS; SCID mouse; T cell receptor; fusion gene; genetic mapping; genetically modified animals; human immunodeficiency virus 1; human subject; laboratory mouse; lymphocyte proliferation; protein sequence; superantigens; virus antigen; virus infection mechanism; virus replication

DESCRIPTION: Superantigens (SA) are microbial glycoproteins that act as potent T cell activators. They bind to major histocompatibility complex (MHC) class II proteins, but T cell recognition of SA is not restricted by MHC alleles, and there is no requirement for antigen processing, as with regular peptide antigens. Typically, alpha-beta T cell antigen receptors (TCR) of T cells responding to a given SA express the same V beta variable region gene products. Thus SA are also called V beta-selective elements. By preparing a panel of monoclonal antibodies to human V beta gene products, the investigators have developed a novel technique for rapid isolation of homogeneous cell lines expressing the same V beta. These IL-2 dependent non- transformed cells were used as targets for HIV-1 infection in vitro. HIV replication measured by gag encoded p24 varied up to 100 fold depending on V beta expression with V beta 12, but not V beta 6.7a cell lines, supporting high level HIV-1 replication of three divergent isolates. This effect is not MHC restricted and can be blocked with anti-MHC class II mAb. Using ex vivo lymphocytes from seropositive donors they found that V beta 12 cells expressed more gp120 and contained more HIV-l DNA than control V beta subsets. Non-T cells from such donors selectively stimulated a V beta 12 cell line and not a V beta 6.7a cell line consistent with expression of a SA. They propose to (l) define the HIV-1 associated SA using divergent and defective viral isolates. In particular, they will use two isolates with different V beta specificity patterns to produce chimeras and map the gene encoding V beta selectivity; and (2) investigate the functional effects of the HIV-l SA. They propose experiments to compare the HIV-V beta selective element to microbial SA, to examine the effects of the possible SA in vivo in HIV-1 seropositive patients, in HIV-l infected hu/SCID mice, and in TCR V beta 12 and TCR V beta 6.7a transgenic mice. They suggest that blocking the effects of an HIV-1 SA in vivo could represent a novel therapeutic approach to AIDS.

描述： 超抗原（SA）是微生物糖蛋白，充当有效的T细胞 激活剂。 它们与主要的组织相容性复合物（MHC）类结合 II蛋白质，但T细胞识别SA不受MHC的限制 等位基因，并且不需要抗原处理 常规肽抗原。 通常，α-βT细胞抗原受体 （TCR）响应给定的SA表达相同的V beta的TCR 可变区域基因产物。 因此，SA也称为Vβ选择性 元素。 通过准备一组对人Vβ基因的单克隆抗体 产品，研究人员开发了一种新型技术来快速 表达相同Vβ的均匀细胞系的分离。 这些 IL-2依赖性非转化细胞用作HIV-1的靶标 体外感染。 通过插科打p24测量的HIV复制变化 根据V Beta 12的V beta表达，最多100倍，而不是V Beta 6.7a细胞系，支持三个的高级HIV-1复制 分离株。 此效果不受MHC的限制，可以阻止 抗MHC II类mab。使用血清阳性的离体淋巴细胞 他们发现V Beta 12单元表达了更多的GP120并包含 HIV-L DNA多于对照Vβ子集。 来自此类供体的非T细胞 有选择地刺激Vβ12单元线，而不是Vβ.7a单元 线与SA的表达一致。 他们建议（l）使用分歧和 病毒分离株有缺陷。 特别是，他们将使用两个分离株 不同的Vβ特异性模式生产嵌合体并绘制 编码Vβ选择性的基因； （2）研究功能 HIV-L SA的影响。 他们提出了比较HIV-V的实验 beta选择性元素对微生物SA，以检查 HIV-1血清阳性患者的体内可能的SA可能会在HIV-L感染中 HU/SCID小鼠，在TCR V Beta 12和TCR V Beta 6.7a转基因小鼠中。 他们建议阻止体内HIV-1 SA的影响 代表一种新型的艾滋病治疗方法。