Association of VH4-59 Antibody Variable Gene Usage with Recognition of an Immunodominant Epitope on the HIV-1 Gag Protein.
Association of VH4-59 Antibody Variable Gene Usage with Recognition of an Immunodominant Epitope on the HIV-1 Gag Protein.
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DOI：
10.1371/journal.pone.0133509
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Crowe JE Jr
中科院分区：
文献类型：
--
作者：
Chukwuma VU;Hicar MD;Chen X;Nicholas KJ;Joyner A;Kalams SA;Landucci G;Forthal DN;Spearman PW;Crowe JE Jr
人类对HIV-1感染的抗体反应识别病毒粒子的不同抗原亚单位，并包括高水平的Gag蛋白抗体。我们在这里报告分离和鉴定在HIV感染者的抗体库中普遍存在的GAG特异性人类单抗(MAbs)的一个子集。由单抗重链可变区VH4-59编码了多个GAG特异性单抗谱系，其中一个有代表性的单抗命名为3E4，它识别GAG p17亚单位球状头部的线性表位。我们没有发现单抗3E4在实验室研究中具有任何功能的证据，这些研究旨在阐明其免疫学活性，包括中和试验、抗体依赖的细胞介导的病毒抑制试验或由Gag-3E4复合体引起的增强T细胞反应的试验。这些发现表明，GAG蛋白中的这个免疫优势表位与VH4-59生殖系基因的使用有关，可能会诱导高水平的B细胞编码结合的但不起作用的抗体，这些抗体在HIV感染后占据了重要的保留空间。这些研究在HIV病毒粒子的免疫分散活动中定义了另一个特定的分子机制。
The human antibody response against HIV-1 infection recognizes diverse antigenic subunits of the virion, and includes a high level of antibodies to the Gag protein. We report here the isolation and characterization of a subset of Gag-specific human monoclonal antibodies (mAbs) that were prevalent in the antibody repertoire of an HIV-infected individual. Several lineages of Gag-specifc mAbs were encoded by a single antibody heavy chain variable region, VH4-59, and a representative antibody from this group designated mAb 3E4 recognized a linear epitope on the globular head of the p17 subunit of Gag. We found no evidence that mAb 3E4 exhibited any function in laboratory studies aimed at elucidating the immunologic activity, including assays for neutralization, Ab-dependent cell-mediated virus inhibition, or enhanced T cell reactivity caused by Gag-3E4 complexes. The findings suggest this immunodominant epitope in Gag protein, which is associated with VH4-59 germline gene usage, may induce a high level of B cells that encode binding but non-functional antibodies that occupy significant repertoire space following HIV infection. The studies define an additional specific molecular mechanism in the immune distraction activity of the HIV virion.