IMMUNE RESPONSE TO HIV SYNTHETIC PEPTIDES

人类免疫缺陷病毒（HIV）， 获得性免疫缺陷综合征（艾滋病）是一种逆转录病毒， 感染某些淋巴细胞亚群， 中枢神经系统组织中的蛋白质。 的 病毒由蛋白质的核衣壳核心组成， 被脂质包膜包围的核糖核酸。 这个信封 含有120，000（gp 120）和41，000（gp 41）分子量 糖蛋白，其来源于母体前体 160，000（gp 160）分子量的糖蛋白。 的一个主要目标 这项研究的目的是确定HIV包膜的抗原区域， 使用合成肽的糖蛋白。 免疫原性肽 将使用含有天然决定簇的基因组， 与蛋白质载体和佐剂组分的复合物， 努力开发一种合成疫苗， 感染后的挑战与传染性艾滋病毒。 初始 gp 160衍生物的推定抗原决定簇的定位 从其主要氨基酸序列的分析， 从包膜基因互补DNA序列预测。 计算机算法将用于预测可能的表位 与GP 160相关。 其中包括Chou-Fasman预测， 蛋白质二级结构特征及Hopp和Woods的应用 将抗原性与序列区域相关联的参数 高亲水性。 来自不同已知的信封序列 还将选择非变异的分离物。 肽将 通过固相方法组装并偶联至蛋白质 用于小鼠和家兔接种的载体。 抗肽 将测定抗血清对肽-蛋白的反应性 沿着与来自细胞的完整包膜糖蛋白的缀合物 被破坏的、感染的淋巴细胞的裂解物。 那些肽 诱导对包膜糖蛋白的抗天然应答将是 选择作为候选疫苗，以及它们诱导 将评估小鼠的回忆应答。 这些抗血清将 也可以在体外测定HIV感染性的中和作用。 一 第二组HIV包膜肽将被筛选， 抑制正常T细胞和B细胞增殖反应的能力 对外界刺激如淋巴因子和有丝分裂原。 这 抑制是一般免疫抑制作用特征 这是针对其他逆转录病毒抗原建立的。 肽 能够抑制这些反应将被调查， 考虑到它们与膜的潜在相互作用， T细胞和B细胞的膜成分。

Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), is a retrovirus which infects certain lymphocyte subpopulations and has been detected in central nervous system tissue of afflicted individuals. The virus is composed of a nucleocapsid core of protein and ribonucleic acid surrounded by a lipid envelope. This envelope contains 120,000 (gp 120) and 41,000 (gp 41) molecular weight glycoproteins, which are derived from the parent precursor 160,000 (gp 160) molecular weight glycoprotein. A major goal of the proposed study is to define antigenic regions of HIV envelope glycoproteins using synthetic peptides. Immunogenic peptides containing native determinants will be used to formulate complexes with protein carriers and adjuvant components in efforts to develop a synthetic vaccine protecting individuals from infection following challenge with infectious HIV. The initial mapping of the putative antigenic determinants of gp 160 derives from analysis of its primary amino acid sequence, which has been predicted from the envelope gene complementary DNA sequence. Computer algorithms will be used to predict possible epitopes associated with gp 160. They include Chou-Fasman prediction of protein secondary structural features and use of Hopp and Woods parameters in correlating antigenicity with sequential regions of high hydrophilicity. Envelope sequences from different known isolates will also be selected which are non-variant. Peptides will be assembled by solid phase methodology and coupled to protein carriers for inoculation of mice and rabbits. Anti-peptide antisera will be assayed for reactivity to peptide-protein conjugates along with intact envelope glycoproteins from cell lysates of disrupted, infected lymphocytes. Those peptides inducing anti-native responses to envelope glycoproteins will be selected as vaccine candidates, and their ability to induce an anamnestic response in mice will be assessed. These antisera will also be assayed for neutralization of HIV infectivity in vitro. A second panel of HIV envelope peptides will be screened for their ability to inhibit normal T- and B-cell proliferative responses toward external stimuli such as lymphokines and mitogens. This inhibition is characteristic of a general immunodepressive effect which has been established for other retroviral antigens. Peptides capable of inhibiting these responses will be investigated with respect to their potential interaction with membranes and membrane components of T- and B-cells.