Hadida F, Haas G, Zimmermann N, Hosmalin A, Spohn R, Samri A, Jung G, Debre P, Autran B
Laboratory for Cellular and Tissue Immunology, University Hospital Center Pitié-Salpétrière, Paris, France.
J Immunol. 1995 Apr 15;154(8):4174-86.
In a previous analysis of HIV-1-specific CTLs in lymphoid organs from HIV-seropositive patients, we reported high frequencies of in vivo differentiated CTLs directed against two immunodominant regions in the central and in the C-terminal part of the HIV-1 Nef protein. The present study analyzes the epitopes recognized by CTLs in the carboxyl terminus of Nef (amino acids 182-205). In addition to several epitopes that are recognized in association with different HLA molecules (A1, A2, A25(10), B35, B52), we defined an optimal nonapeptide (190-198). This nonapeptide was recognized by CTLs down to nanomolar concentrations in the context of at least two HLA molecules, HLA-B52 and HLA-A2, including three HLA-A2 subtypes: HLA-A2.1, -A2.2, and -A2.4. We also determined the relative frequencies of effector CTLs directed against peptide 190-198 to be as high as 10(-4), as opposed to lower frequencies ranging between 5 x 10(-5) and 5 x 10(-6) observed for the other peptides recognized in the same region, thus confirming the optimal presentation of this nonapeptide in vivo. Molecular modeling of the interactions between HLA-A2.1 and Nef peptide 190-198 suggests the formation of a stable complex and allowed us to study sequence motifs that are important for the binding of the HIV-1 peptide in the pockets of the HLA-A2.1 molecule.
在先前对HIV血清阳性患者淋巴器官中HIV-1特异性CTL的分析中，我们报告了针对HIV-1 Nef蛋白中央和C末端两个免疫显性区域的体内分化CTL的高频率。本研究分析了Nef羧基末端（氨基酸182-205）中CTL识别的表位。除了与不同HLA分子（A1、A2、A25(10)、B35、B52）结合识别的几个表位外，我们还确定了一个最佳九肽（190-198）。在至少两种HLA分子HLA-B５２和HLA-A2的背景下，包括三种HLA-A2亚型：HLA-A2.1、-A2.2和-A2.4，该九肽在纳摩尔浓度下就能被CTL识别。我们还确定了针对肽190-198的效应CTL的相对频率高达10(-4)，而在同一区域识别的其他肽的频率则在5×10(-5)至5×10(-6)之间，从而证实了该九肽在体内的最佳呈递。HLA-A2.1与Nef肽190-198之间相互作用的分子模型表明形成了稳定的复合物，并使我们能够研究对于HIV-1肽在HLA-A2.1分子口袋中结合很重要的序列基序。
