HELPER T-CELL ANTIGENIC SITE IDENTIFICATION IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME VIRUS GP120 ENVELOPE PROTEIN AND INDUCTION OF IMMUNITY IN MICE TO THE NATIVE PROTEIN USING A 16-RESIDUE SYNTHETIC PEPTIDE
HELPER T-CELL ANTIGENIC SITE IDENTIFICATION IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME VIRUS GP120 ENVELOPE PROTEIN AND INDUCTION OF IMMUNITY IN MICE TO THE NATIVE PROTEIN USING A 16-RESIDUE SYNTHETIC PEPTIDE
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DOI：
10.1073/pnas.84.12.4249
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发表时间：
1987-06-01
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：
CEASE, KB;MARGALIT, H;BERZOFSKY, JA
许多研究致力于分析获得性免疫缺陷综合征病毒抗原的抗体，但据我们所知，还没有研究确定引起T细胞免疫的病毒抗原位点，尽管这种免疫在保护免受许多其他病毒的侵害方面很重要。T细胞倾向于仅识别蛋白质抗原上有限数量的离散位点。对免疫缺陷辅助T细胞位点的分析表明，这些位点倾向于形成两亲性螺旋。基于该模型的算法被用来确定两个候选的T细胞位点，env T1和env T2，在包膜蛋白的人类T淋巴细胞嗜性病毒IIIB型，在其他人类免疫缺陷病毒分离株保守。合成相应的肽，并在遗传定义的近交系小鼠和F1小鼠中研究其诱导淋巴结增殖。用426个残基的重组包膜蛋白片段免疫后，在研究的两个F1组合中观察到对天然gp120以及对每种肽的显著反应。相反，免疫与env T1肽诱导T细胞免疫的天然gp120包膜蛋白。进一步检查了对env T1肽的反应的遗传学，并在测试的四个独立的主要组织相容性单倍型中的三个中显示出显著的反应，这表明人群中的高频反应。辅助性T细胞位点的鉴定应有助于开发诱导T细胞和B细胞免疫的高免疫原性、无载体疫苗。通过用16个残基的肽免疫引起对天然病毒蛋白的T细胞免疫的能力表明，这些位点代表了获得性免疫缺陷综合征的有效疫苗的潜在重要组分。
Much effort has been devoted to the analysis of antibodies to acquired immunodeficiency syndrome virus antigens, but no studies, to our knowledge, have defined antigenic sites of the virus that elicit T-cell immunity, even though such immunity is important in protection against many other viruses. T cells tend to recognize only a limited number of discrete sites on a protein antigen. Analysis of immunodeficiency helper T-cell sites has suggested that such sites tend to form amphipathic helices. An algorithm based on this model was used to identify two candidate T-cell sites, env T1 and env T2, in the envelope protein of human T-lymphotropic virus type IIIB that were conserved in other human immunodeficiency virus isolates. Corresponding peptides were synthesized and studied in genetically defined inbred and F1 mice for induction of lymph node proliferation. After immunization with a 426-residue recombinant envelope protein fragment, significant responses to native gp120, as well as to each peptide, were observed in both F1 combinations studied. Conversely, immunization with env T1 peptide induced T-cell immunity to the native gp120 envelope protein. The genetics of the response to env T1 peptide were further examined and revealed a significant response in three of four independent major histocompatibility haplotypes tested, an indication of high frequency responsiveness in the population. Identification of helper T-cell sites should facilitate development of a highly immunogenic, carrier-free vaccine that induces T-cell and B-cell immunity. The ability to elicit T-cell immunity to the native viral protein by immunization with a 16-residue peptide suggests that such sites represent potentially important components of an effective vaccine for acquired immunodeficiency syndrome.