An autonomous CDR3δ is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by γδ T cells
An autonomous CDR3δ is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by γδ T cells
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DOI：
10.1038/ni.1620
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发表时间：
2008-07-01
影响因子：
30.5
通讯作者：
Garcia, K. Christopher
中科院分区：
文献类型：
--
作者：
Adams, Erin J.;Strop, Pavel;Garcia, K. Christopher
目前尚不清楚γ δ T细胞抗原受体（TCR）是否以类似于抗体或α β TCR的方式检测抗原。在这里，我们表明，G8和KN 6 γ δ TCR和主要组织相容性复合物Ib类分子T22之间的反应性可以重现，保留野生型配体亲和力，在α β TCR移植后，G8或KN 6互补决定区3-δ（CDR 3 δ）环代替α β TCR的CDR 3 α环。我们还发现，所有T22反应性γ δ TCR的CDR 3 δ环中的共享序列基序以能量不同的方式结合T22，并且以弱亲和力结合G8的T10（d）通过单点突变转化为高亲和力配体。我们的研究结果证明了单个CDR 3环在抗原识别中的前所未有的自主性。
It remains unclear whether gamma delta T cell antigen receptors (TCRs) detect antigens in a way similar to antibodies or alpha beta TCRs. Here we show that reactivity between the G8 and KN6 gamma delta TCRs and the major histocompatibility complex class Ib molecule T22 could be recapitulated, with retention of wild-type ligand affinity, in an alpha beta TCR after grafting of a G8 or KN6 complementarity-determining region 3-delta (CDR3 delta) loop in place of the CDR3 alpha loop of an alpha beta TCR. We also found that a shared sequence motif in CDR3 delta loops of all T22-reactive gamma delta TCRs bound T22 in energetically distinct ways, and that T10(d), which bound G8 with weak affinity, was converted into a high-affinity ligand by a single point mutation. Our results demonstrate unprecedented autonomy of a single CDR3 loop in antigen recognition.