Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties
Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties
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DOI：
10.1016/j.immuni.2004.09.008
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发表时间：
2004-11-01
期刊：
影响因子：
32.4
通讯作者：
McHeyzer-Williams, MG
中科院分区：
文献类型：
--
作者：
Malherbe, L;Hausl, C;McHeyzer-Williams, MG
聚焦于应答克隆的TCR库的辅助T细胞应答提供了体内克隆选择机制的实验途径。使用TCRP链动物，我们直接评估TCR α CDR 3多样性的程度和单个抗原特异性Th细胞的pMHCII结合属性。在这里，我们证明了显性克隆型，定义的TCR连接序列的相似性，是令人惊讶的不同的水平上的pMHCII结合特性，抗原暴露前后。在免疫应答期间，我们可以检测和量化表达低亲和力TCR的抗原特异性克隆型的选择性损失。该亲和力阈值选择之后是优选克隆型的无偏繁殖，而不管TCR-pMHCII半衰期或亲和力。因此，亲和力阈值机制区分具有最佳拟合的TCR的Th克隆，并在不促进自身反应性的情况下传播克隆多样性。
Helper T cell responses that focus the TCR repertoire of responding clones provide experimental access to the mechanisms of clonal selection in vivo. Using TCRP chain animals, we directly evaluate the extent of TCRalpha CDR3 diversity and the pMHCII binding attributes of individual antigen-specific Th cells. Here, we demonstrate that dominant clonotypes, as defined by TCR junctional sequence similarities, are surprisingly diverse at the level of pMHCII binding properties, before and after antigen exposure. During an immune response, we can detect and quantify the selective loss of antigen-specific clonotypes that express lower-affinity TCR. This affinity threshold selection is followed by the unbiased propagation of preferred clonotypes regardless of TCR-pMHCII half-lives or affinity. Thus, an affinity threshold mechanism discriminates Th clones with TCR of best fit and propagates clonal diversity without promoting autoreactivity.