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An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes.

机译:人类免疫缺陷病毒包膜糖蛋白gp160的免疫优势表位,被I类主要组织相容性复合物分子限制的鼠细胞毒性T淋巴细胞识别。

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摘要

Because cytotoxic T lymphocytes (CTL) may be important for preventing direct cell-to-cell transmission of human immunodeficiency virus (HIV), the agent responsible for acquired immunodeficiency syndrome, we have begun to investigate the epitope specificity and immune response (Ir) gene control of anti-HIV CTL responses in experimental animals. Mice were infected with a recombinant vaccinia virus expressing the HIV gp160 envelope gene, and the primed lymphocytes were restimulated in vitro with a transfected histocompatible cell line expressing the same gene. Our results show that H-2d mice are CTL high responders and H-2k mice are low responders to the HIV gp160 envelope protein under these conditions. Moreover, the H-2d mice respond predominantly to a single immunodominant site represented by a 15-residue synthetic peptide conforming to the amphipathic alpha-helix model of T-cell epitopes and seen by CD4- CD8+ CTL in association with the Dd class I major histocompatibility complex (MHC) molecules. The facts that CTL responses were detected in the context of only one of four class I MHC molecules tested and that the response was limited predominantly to a single epitope indicate that the CTL repertoire elicited by the HIV envelope protein in association with murine class I MHC molecules may be very limited. In addition, this epitope occurs in a highly variable segment of the envelope protein. This puts constraints on the use of a single peptide sequence from this region in a vaccine, as such a vaccine would have to be polyvalent. Nevertheless, this same variability suggests that this region may be under selective pressure from human CTL, and therefore that this site may be immunodominant in humans as well as mice and so of clinical importance in vaccine development.
机译:由于细胞毒性T淋巴细胞(CTL)对于预防人类免疫缺陷病毒(HIV)的直接细胞间传播可能是重要的,人类免疫缺陷病毒(HIV)是导致获得性免疫缺陷综合征的因素,因此我们已经开始研究表位特异性和免疫应答(Ir)基因在实验动物中控制抗HIV CTL反应。用表达HIV gp160包膜基因的重组牛痘病毒感染小鼠,并用表达该基因的转染的组织相容性细胞系在体外重新刺激初免的淋巴细胞。我们的结果表明,在这些条件下,H-2d小鼠对HIV gp160包膜蛋白具有CTL高应答性,而H-2k小鼠具有低应答性。此外,H-2d小鼠主要对由15个残基的合成肽表示的单个免疫显性位点作出反应,该肽与T细胞表位的两亲性α-螺旋模型相符,并由CD4-CD8 + CTL与Dd I类主要抗体相关组织相容性复合物(MHC)分子。仅在所测试的四个I类MHC分子中检测到CTL反应的事实,并且该反应主要限于单个表位这一事实表明,HIV包膜蛋白与鼠I类MHC分子相关联引发了CTL谱表可能非常有限。另外,该表位出现在包膜蛋白的高度可变区段中。这就限制了疫苗中来自该区域的单个肽序列的使用,因为这种疫苗必须是多价的。但是,这种相同的可变性表明该区域可能处于人CTL的选择性压力之下,因此该位点在人类以及小鼠中可能具有免疫优势,因此在疫苗开发中具有临床重要性。

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