Sequence and functional characterization of a public HIV-specific antibody clonotype.

Sequence and functional characterization of a public HIV-specific antibody clonotype.
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DOI:
10.1016/j.isci.2021.103564
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发表时间:
2022-01-21
期刊:
影响因子:
5.8
通讯作者:
Georgiev IS
Georgiev IS
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Murji AA;Raju N;Qin JS;Kaldine H;Janowska K;Fechter EF;Mapengo R;Scheepers C;Setliff I;Acharya P;Morris L;Georgiev IS

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已经鉴定了几种病原体的多个个体之间共享的公共抗体克隆型。然而,很少有人知道的决定因素抗体的“公共性”。在这里,我们的特点的序列和功能特性的抗体从一个公共克隆型靶向的CD 4结合位点的HIV-1 Env。我们的研究结果表明,HIV-1特异性的公共抗体在这里研究,包括从三个人的序列,调制的VH,但不是VL,生殖系基因。来自不同个体的公共重链和轻链的非天然配对表明该公共抗体克隆型内序列的功能互补。抗原识别的强度似乎取决于所用的特异性抗体轻链,但不取决于其他序列特征,如天然抗体或种系序列同一性。了解抗体克隆型“公共性”的决定因素,可以提供深入了解宿主-病原体相互作用的基本规则,在人口水平上,与克隆型特异性疫苗的发展的影响。影响公共克隆型抗原特异性的定义的抗体特征公共抗体在供体内和供体之间表现出高度的序列相似性揭示了来自不同供体的重链和轻链的功能互补免疫学;病毒学
Public antibody clonotypes shared among multiple individuals have been identified for several pathogens. However, little is known about the determinants of antibody “publicness”. Here, we characterize the sequence and functional properties of antibodies from a public clonotype targeting the CD4 binding site on HIV-1 Env. Our results showed that HIV-1 specificity for the public antibodies studied here, comprising sequences from three individuals, was modulated by the VH, but not VL, germline gene. Non-native pairing of public heavy and light chains from different individuals suggested functional complementation of sequences within this public antibody clonotype. The strength of antigen recognition appeared to be dependent on the specific antibody light chain used, but not on other sequence features such as native-antibody or germline sequence identity. Understanding the determinants of antibody clonotype “publicness” can provide insights into the fundamental rules of host-pathogen interactions at the population level, with implications for clonotype-specific vaccine development. Defined antibody features that affect the antigen specificity of a public clonotype Public antibodies exhibited high sequence similarity both within and among donors Revealed functional complementation of heavy and light chains from different donors Immunology; Virology
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