Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.
Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.
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DOI：
10.1371/journal.pone.0016857
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发表时间：
2011-03-30
期刊：
影响因子：
3.7
通讯作者：
Scott JK
中科院分区：
文献类型：
--
作者：
Breden F;Lepik C;Longo NS;Montero M;Lipsky PE;Scott JK
HIV-1感染过程中产生的抗体（Abs）很少能中和广泛的病毒分离株;仅分离出8种广泛中和（bNt）单克隆（M）Abs。然而，为了有效，HIV-1疫苗可能必须引出这些单克隆抗体的基本特征。所有这些bNt单克隆抗体的V基因都是高度体细胞突变的，其中5个的VH基因编码长（≥20 aa）的第三互补决定区（CDR-H3）。这使我们质疑长CDR-H3和高水平的体细胞突变（SM）是否是抗HIV bNt MAb的优选特征，或者其他适应性免疫应答是否通常会引发它们。我们从慢性（病毒）感染（ChI）、急性（细菌和病毒）感染（AcI）和系统性自身免疫性疾病（SAD）中分离的700多个已知抗原特异性的人单克隆抗体中组装了VH基因序列数据库，并比较了它们的CDR-H3长度、SM数量和种系VH基因使用。我们发现，抗HIV抗体，无论其中和宽度如何，往往具有较长的CDR-H3和大量的SM。然而，这些特征在与其他慢性病毒感染相关的抗体中也很常见。相比之下，来自急性病毒感染（而非细菌感染）的Ab倾向于具有相对短的CDR-H3和低数目的SM，而SAD Ab通常在CDR-H3长度和SM数目方面居中。VH基因使用的分析表明，ChI抗体也倾向于有利于远端生殖系VH基因（特别是VH 1 -69），特别是在携带长CDR-H3的抗体中。在慢性病毒感染与急性病毒感染期间产生的Ab之间的显著差异表明，在持续感染期间可以优先选择携带长CDR-H3、高水平SM和VH 1 -69基因使用的Ab。
Antibodies (Abs) produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt) monoclonal (M)Abs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the VH genes of five of them encode a long (≥20 aa) third complementarity-determining region (CDR-H3). This led us to question whether long CDR-H3s and high levels of somatic mutation (SM) are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. We assembled a VH-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral) infections (ChI), acute (bacterial and viral) infections (AcI), and systemic autoimmune diseases (SAD), and compared their CDR-H3 length, number of SMs and germline VH-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections) tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of VH gene usage showed that ChI Abs also tended to favor distal germline VH-genes (particularly VH1-69), especially in Abs bearing long CDR-H3s. The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and VH1-69 gene usage may be preferentially selected during persistent infection.
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
3.7
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BRAUN, J
影响因子：
4.6
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Goldblatt, D.
影响因子：
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de Wildt, RMT;van Venrooij, WJ;Tomlinson, IN
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