Février M, Boudet F, Deslandres A, Theze J
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
AIDS Res Hum Retroviruses. 1995 Apr;11(4):491-500.
Two human IgGk monoclonal antibodies (HuMAbs), termed 48-16 and 50-61A, were derived by Epstein-Barr virus transformation of B cells from two HIV-1-infected donors. These HuMAbs recognized discrete, nonoverlapping, and conformational or discontinuous epitopes on the gp120 envelope protein of HIV-1. The binding affinities of 48-16 and 50-61A for recombinant gp120 from HIV-1LAI strain, reflected by their dissociation constants, were estimated to be 2-5 x 10(-9) and 2.4 x 10(-10) M, respectively. 48-16 was shown to react with a conserved determinant present on a variety of divergent laboratory isolates, residing outside the CD4-binding site and the V3 region, which remains to be determined. 48-16 did not display, however, any detectable functional activity. 50-61A exhibited a more restricted recognition pattern, but was able to completely inhibit the 2 HIV-1 laboratory strains LAI and SF2 in a concentration range of 0.5-10 micrograms/ml, as measured by an antigen capture assay. The ability of 50-61A to block the interaction between recombinant gp120LAI and recombinant as well as cellular CD4 indicated that 50-61A epitope was localized near or within the CD4-binding side. We also demonstrated that 50-61A- and 48-16-defined epitopes (or closely related epitopes) were immunogenic in infected humans, since serum samples from 45 seropositive subjects were able to inhibit both gp120LAI-HuMAb recognitions. However, the presence of "50-61A-like" antibodies in these sera could not be associated with their neutralizing activities of HIV-1LAI infection. Interest in producing such antibodies for characterization of the human B cell repertoire to HIV-1 and their potential use in passive immunotherapy or vaccination strategy against AIDS are discussed.
两种人IgGk单克隆抗体（HuMAbs），分别称为48 - 16和50 - 61A，是通过对两名HIV - 1感染供体的B细胞进行爱泼斯坦 - 巴尔病毒转化而获得的。这些HuMAbs识别HIV - 1的gp120包膜蛋白上离散的、不重叠的、构象性或不连续的表位。48 - 16和50 - 61A对HIV - 1 LAI株重组gp120的结合亲和力，由它们的解离常数反映，估计分别为2 - 5×10（-9）和2.4×10（-10）M。48 - 16被证明与存在于多种不同实验室分离株上的一个保守决定簇反应，该决定簇位于CD4结合位点和V3区域之外，其具体位置尚待确定。然而，48 - 16未表现出任何可检测到的功能活性。50 - 61A表现出更具限制性的识别模式，但通过抗原捕获试验测定，在0.5 - 10微克/毫升的浓度范围内能够完全抑制两种HIV - 1实验室株LAI和SF2。50 - 61A阻断重组gp120LAI与重组以及细胞CD4之间相互作用的能力表明，50 - 61A表位位于CD4结合位点附近或之内。我们还证明，50 - 61A和48 - 16定义的表位（或密切相关的表位）在受感染人类中具有免疫原性，因为来自45名血清阳性受试者的血清样本能够抑制gp120LAI - HuMAb的两种识别。然而，这些血清中“50 - 61A样”抗体的存在与其对HIV - 1 LAI感染的中和活性并无关联。文中讨论了生产此类抗体用于表征人类针对HIV - 1的B细胞库及其在艾滋病被动免疫疗法或疫苗接种策略中的潜在用途的意义。
