Khalife J, Guy B, Capron M, Kieny M P, Ameisen J C, Montagnier L, Lecocq J P, Capron A
Centre d'Immunologie et de Biologie Parasitaire, Institut Pasteur, Lille, France.
AIDS Res Hum Retroviruses. 1988 Feb;4(1):3-9. doi: 10.1089/aid.1988.4.3.
HIV-infected individuals progress toward AIDS despite the early elicitation of a specific immune response. Analysis of the isotypic distribution of HIV-specific antibodies appears of special interest for two reasons: first, isotypic diversity is partly under the control of antigen-specific T-helper cells, the very cells infected by HIV; second, isotype determines antibody functions, effector (neutralization, antibody-dependent complement, or cell-mediated cytotoxicity) as well as blocking functions. We have investigated by Western blot analysis the isotypic profile of the antibody response to HIV structural proteins (env, gag, pol) and to the nonstructural protein F (3' orf), which is absent from the virion and might primarily target infected cells. In 115 asymptomatic individuals, infected by sexual contact (homosexual men) or intravenously (hemophiliacs), the response to gag-products was polyisotypic, including IgM, IgG1, IgG3 and IgA; the response to F was more restricted (IgM, IgG1, IgA) and the response to env strikingly restricted to the IgG1 isotype, suggesting different regulatory mechanisms in the B-cell response to these proteins. The isotypic distribution was also influenced by the route of infection, IgG4 and IgE (gag-specific) being exclusively elicited in the hemophiliac group. Finally, observations of potential diagnostic interest were made in a limited number of at-risk individuals; these included the presence of gag- and pol-specific IgM or IgA in the absence of any HIV-specific IgG isotypes; and the presence of gag- and F-specific antibodies in the absence of env-specific antibodies, suggesting the early occurrence of both isotypic and antigenic selection mechanisms during the course of HIV infection.
尽管早期引发了特异性免疫反应，但感染艾滋病毒的个体仍会发展为艾滋病。对艾滋病毒特异性抗体的同种型分布进行分析似乎特别有意义，原因有两个：第一，同种型多样性部分受抗原特异性辅助性T细胞控制，而这些细胞正是被艾滋病毒感染的细胞；第二，同种型决定抗体功能，包括效应功能（中和、抗体依赖性补体或细胞介导的细胞毒性）以及阻断功能。我们通过蛋白质印迹分析研究了针对艾滋病毒结构蛋白（env、gag、pol）和非结构蛋白F（3' 开放阅读框）的抗体反应的同种型谱，非结构蛋白F不存在于病毒颗粒中，可能主要靶向被感染的细胞。在115名通过性接触感染（男同性恋者）或静脉注射感染（血友病患者）的无症状个体中，对gag产物的反应是多同种型的，包括IgM、IgG1、IgG3和IgA；对F的反应更具局限性（IgM、IgG1、IgA），而对env的反应则显著局限于IgG1同种型，这表明B细胞对这些蛋白质的反应存在不同的调节机制。同种型分布也受感染途径的影响，IgG4和IgE（gag特异性）仅在血友病患者组中引发。最后，在少数高危个体中进行了具有潜在诊断意义的观察；这些观察包括在没有任何艾滋病毒特异性IgG同种型的情况下存在gag和pol特异性IgM或IgA；以及在没有env特异性抗体的情况下存在gag和F特异性抗体，这表明在艾滋病毒感染过程中同种型和抗原选择机制均早期出现。
