Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site
Nonneutralizing antibodies to the CD4-binding site on the gp120 subunit of human immunodeficiency virus type 1 do not interfere with the activity of a neutralizing antibody against the same site
复制标题
DOI：
10.1128/jvi.77.2.1084-1091.2003
复制
发表时间：
2003-01-01
影响因子：
5.4
通讯作者：
Moore, JP
中科院分区：
文献类型：
--
作者：
Herrera, C;Spenlehauer, C;Moore, JP
我们研究了针对人类免疫缺陷病毒1型（HIV - 1）包膜糖蛋白（Env）复合物的gp120亚单位的非中和性单克隆抗体（MAb）是否会干扰另一种抗gp120单克隆抗体对HIV - 1的中和作用。我们使用了针对gp120上与CD4结合位点（CD4BS）重叠的表位簇的中和性（b12）和非中和性（205 - 42 - 15、204 - 43 - 1、205 - 46 - 9）单克隆抗体。所有单克隆抗体，无论是中和性的还是非中和性的，都相互竞争与单体gp120的结合，这表明它们的表位在拓扑结构上非常接近。然而，非中和性的CD4BS单克隆抗体并不干扰单克隆抗体b12的中和活性。相反，在使用Env转染细胞表面表达的寡聚Env进行的结合试验中，非中和性单克隆抗体确实在一定程度上与b12竞争Env结合。Env转染细胞的表面包含两类针对CD4BS单克隆抗体的结合位点。一种类型的位点可被b12和非中和性CD4BS单克隆抗体识别；另一种仅被b12识别。基于使用单体gp120或Env转染细胞进行的Env - gp120相互作用的结合试验并不能预测HIV - 1中和试验的结果，因此在评估抗Env单克隆抗体的特性时应谨慎使用。
We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the gp120 subunit of the envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 (HIV-1) can interfere with HIV-1 neutralization by another anti-gp120 MAb. We used neutralizing (b12) and nonneutralizing (205-42-15, 204-43-1, 205-46-9) MAbs to the epitope cluster overlapping the CD4-binding site (CD4BS) on gp120. All the MAbs, neutralizing or otherwise, cross-competed for binding to monomeric gp120, indicating the close topological proximity of their epitopes. However, the nonneutralizing CD4BS MAbs did not interfere with the neutralization activity of MAb b12. In contrast, in a binding assay using oligomeric Env expressed on the surface of Env-transfected cells, the nonneutralizing MAbs did partially compete with b12 for Env binding. The surface of Env-transfected cells contains two categories of binding site for CD4BS MAbs. One type of site is recognized by both b12 and nonneutralizing CD4BS MAbs; the other is recognized by only b12. Binding assays for Env-gp120 interactions based on the use of monomeric gp120 or Env-transfected cells do not predict the outcome of HIV-1 neutralization assays, and they should therefore be used only with caution when gauging the properties of anti-Env MAbs.