AN IMMUNODOMINANT EPITOPE OF THE HUMAN IMMUNODEFICIENCY VIRUS ENVELOPE GLYCOPROTEIN GP160 RECOGNIZED BY CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE-RESTRICTED MURINE CYTO-TOXIC LYMPHOCYTES-T
AN IMMUNODOMINANT EPITOPE OF THE HUMAN IMMUNODEFICIENCY VIRUS ENVELOPE GLYCOPROTEIN GP160 RECOGNIZED BY CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE-RESTRICTED MURINE CYTO-TOXIC LYMPHOCYTES-T
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DOI：
10.1073/pnas.85.9.3105
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发表时间：
1988-05-01
影响因子：
11.1
通讯作者：
BERZOFSKY, JA
中科院分区：
文献类型：
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作者：
TAKAHASHI, H;COHEN, J;BERZOFSKY, JA
由于细胞毒性T淋巴细胞(CTL)对于防止人类免疫缺陷病毒(HIV)在细胞间的直接传播可能起重要作用，因此我们已经开始在实验动物中研究抗HIV CTL反应的表位特异性和免疫反应(Ir)基因控制。用表达HIV gp160外膜基因的重组痘苗病毒感染小鼠，并用表达该基因的组织相容细胞系在体外对预置淋巴细胞进行再刺激。我们的结果表明，在这些条件下，H-2d小鼠是CTL高反应者，H-2k小鼠是HIV gp160囊膜蛋白的低反应者。此外，H-2d小鼠主要对单个免疫优势部位做出反应，该部位由15个残基的合成肽代表，符合T细胞表位的两亲性α-螺旋模型，并由与DD-I类主要组织相容性复合体(MHC)分子相关的CD4-CD8+CTL看到。CTL反应仅在所测试的四个I类MHC分子中的一个被检测到，并且该反应主要限于单个表位，这表明由HIV包膜蛋白与小鼠I类MHC分子相关联的CTL谱系可能是非常有限的。此外，这个表位存在于包膜蛋白的一个高度可变的片段中。这限制了疫苗中使用该区域的单一多肽序列，因为这样的疫苗必须是多价的。然而，这种相同的变异性表明该区域可能受到来自人类CTL的选择压力，因此该区域可能在人类和小鼠中具有免疫优势，因此在疫苗开发中具有临床重要性。
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.