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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >AMINO-TERMINAL ALTERATION OF THE HLA-A-ASTERISK-0201-RESTRICTED HUMAN IMMUNODEFICIENCY VIRUS POL PEPTIDE INCREASES COMPLEX STABILITY AND IN VITRO IMMUNOGENICITY
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AMINO-TERMINAL ALTERATION OF THE HLA-A-ASTERISK-0201-RESTRICTED HUMAN IMMUNODEFICIENCY VIRUS POL PEPTIDE INCREASES COMPLEX STABILITY AND IN VITRO IMMUNOGENICITY

机译：HLA-A-ASTERISK-0201限制的人类免疫缺陷病毒POL肽的氨基末端改变可提高复杂稳定性和体外免疫原性

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Initial studies suggested that major histocompatibility complex class I-restricted viral epitopes could be predicted by the presence of particular residues termed anchors, However, recent studies showed that nonanchor positions of the epitopes are also significant for class I binding and recognition by cytotoxic T lymphocytes (CTLs). We investigated if changing nonanchor amino acids could increase class I affinity, complex stability, and T-cell recognition of a natural viral epitope, This concept was tested by using the HLA-A*0201-restricted human immunodeficiency virus type 1 epitope from reverse transcriptase (pol). Position 1 (P1) amino acid substitutions were emphasized because P1 alterations may not alter the T-cell receptor interaction. The peptide with the P1 substitution of tyrosine for isoleucine (I1Y) showed a binding affinity for HLA-A*0201 similar to that of the wild-type pol peptide in a cell lysate assembly assay, Surprisingly, I1Y significantly increased the HLA-A*0201-peptide complex stability at the cell surface, I1Y sensitized HLA-A*0201-expressing target cells for wild-type pol-specific CTL lysis as well as wild-type pol. Peripheral blood lymphocytes from three HLA-A2 HIV-seropositive individuals were stimulated in vitro with I1Y and wild-type pol. I1Y stimulated a higher wild-type pol-specific CTL response than wild-type pol in all three donors. Thus, I1Y may be an ''improved'' epitope for use as a CTL-based human immunodeficiency virus vaccine component, The design of improved epitopes has important ramifications for prophylaxis and therapeutic vaccine development. [References: 24]
机译：最初的研究表明，可以通过存在称为锚的特定残基来预测主要的组织相容性复杂的I类限制性病毒表位。 CTL）。我们研究了改变非锚氨基酸是否可以增加I类亲和力，复杂的稳定性以及对天然病毒表位的T细胞识别。通过使用HLA-A * 0201限制性人类免疫缺陷病毒1型表位（来自逆转录酶）来测试该概念（波尔）。强调了位置1（P1）的氨基酸取代，因为P1的改变可能不会改变T细胞受体的相互作用。 P1酪氨酸替代异亮氨酸（I1Y）的肽与HLA-A * 0201的结合亲和力与野生型pol肽在细胞裂解液组装测定中的相似，令人惊讶的是，I1Y显着增加了HLA-A * 0201肽复合物在细胞表面的稳定性，I1Y致敏的表达HLA-A * 0201的靶细胞用于野生型pol特异性CTL裂解以及野生型pol。在体外用I1Y和野生型pol刺激了来自3个HLA-A2 HIV阳性的个体的外周血淋巴细胞。在所有三个供体中，I1Y刺激的野生型pol特异性CTL反应均高于野生型pol。因此，I1Y可能是用作基于CTL的人类免疫缺陷病毒疫苗组分的“改良”表位。改良表位的设计对预防和治疗性疫苗开发具有重要意义。 [参考：24]

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