IMMUNE RESPONSE TO HIV SYNTHETIC PEPTIDES

人类免疫缺陷病毒(HIV)，引起 获得性免疫缺陷综合征(AIDS)，是一种逆转录病毒 感染某些淋巴细胞亚群，并已被检测到 在患病个体的中枢神经系统组织中。这个 病毒由蛋白质的核衣壳核心和 被脂质包膜包裹的核糖核酸。这个信封 含有120,000(GP 120)和41,000(GP 41)分子量 来自母体前体的糖蛋白 分子量为160,000(GP 160)的糖蛋白。的一个主要目标 建议的研究是定义HIV包膜的抗原区 使用合成肽的糖蛋白。免疫原肽 将使用包含原生决定因素的公式 含蛋白质载体和佐剂组分的复合体 努力开发一种合成疫苗，以保护个人免受 在挑战传染性艾滋病毒之后的感染。首字母 推测的GP 160抗原决定簇的作图 从对其初级氨基酸序列的分析中，它已经被 从包膜基因预测互补的DNA序列。 将使用计算机算法来预测可能的表位 与GP 160相关联。其中包括周-法斯曼对 Hopp和Wood的蛋白质二级结构特征及其应用 抗原性与病毒序列区域相关的参数 高亲水性。来自不同已知的包络序列 也将选择非变种的分离株。多肽将 通过固相方法组装并偶联到蛋白质上 用于接种小鼠和兔子的载体。抗肽 将检测抗血清对多肽-蛋白质的反应性 与细胞中完整的包膜糖蛋白结合在一起 被破坏的、受感染的淋巴细胞的裂解物。那些多肽 诱导对包膜糖蛋白的抗天然应答将是 被选为候选疫苗，以及他们诱导 将评估小鼠的记忆反应。这些抗血清将 也可用于体外中和HIV感染性的检测。一个 将对第二组HIV包膜多肽进行筛查 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 抑制是一种全身免疫抑制效应的特征。 这是为其他逆转录病毒抗原建立的。肽类 能够抑制这些反应的研究将与 关于它们与膜的潜在相互作用和 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.