Burastero S E, Gaffi D, Lopalco L, Tambussi G, Borgonovo B, De Santis C, Abecasis C, Robbioni P, Gasparri A, Lazzarin A, Celada F, Siccardi A G, Beretta A
San Raffaele Scientific Institute, Milan, Italy.
AIDS Res Hum Retroviruses. 1996 Mar 1;12(4):273-80. doi: 10.1089/aid.1996.12.273.
The aim of this study was to investigate the presence and the fine specificity of anti-CD4 autoantibodies in seronegative subjects sexually exposed to HIV-1. Anti-CD4 autoantibodies were previously detected in a fraction of HIV-1-seropositive individuals. Whole sera, purified IgG fractions, and supernatants of EBV-transformed lymphoblastoid cell lines were analyzed by means of ELISA, Western blot, and by competition assays using monoclonal antibodies with known fine specificities. Anti-CD4 antibodies were found in 6 of 18 individuals exposed to HIV-1 infection and who have been persistently seronegative. These antibodies inhibited HIV-1-driven syncytium formation, did not interfere with the CD4-gp120 interaction, and competed for CD4 binding with two of three anti-CD4 monoclonals with known fine specificities. Moreover, autoantibodies with the same fine specificities were found in the supernatants of oligoclonal EBV-transformed B cell lines derived from these individuals. At variance, in the HIV-1-positive patients included in our study, the anti-CD4 antibody response was directed to a broader panel of epitopes, including those involved in CD4-gp120 interactions. In conclusion, anti-CD4 antibodies specific for defined epitopes of the CD4 molecule are generated in the course of an early immune response to HIV-1 antigens in the absence of other signs of infection, as they can be detected by conventional methods. These autoantibodies may play a protective role either alone or in association with other cellular and humoral factors.
本研究的目的是调查性接触过HIV-1的血清阴性个体中抗CD4自身抗体的存在情况及其精细特异性。先前在一部分HIV-1血清阳性个体中检测到了抗CD4自身抗体。通过酶联免疫吸附测定（ELISA）、蛋白质印迹法以及使用具有已知精细特异性的单克隆抗体的竞争试验，对全血清、纯化的IgG组分以及EB病毒转化的淋巴母细胞系的上清液进行了分析。在18名接触过HIV-1感染且一直保持血清阴性的个体中，有6人发现了抗CD4抗体。这些抗体抑制HIV-1驱动的合胞体形成，不干扰CD4与gp120的相互作用，并与三种具有已知精细特异性的抗CD4单克隆抗体中的两种竞争CD4结合。此外，在源自这些个体的寡克隆EB病毒转化的B细胞系的上清液中发现了具有相同精细特异性的自身抗体。与此不同的是，在我们研究纳入的HIV-1阳性患者中，抗CD4抗体反应针对更广泛的表位，包括那些参与CD4与gp120相互作用的表位。总之，在对HIV-1抗原的早期免疫反应过程中，在没有其他感染迹象的情况下，会产生针对CD4分子特定表位的抗CD4抗体，因为它们可以通过传统方法检测到。这些自身抗体可能单独或与其他细胞和体液因子一起发挥保护作用。
