The Shaping of T Cell Receptor Recognition by Self-Tolerance
The Shaping of T Cell Receptor Recognition by Self-Tolerance
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DOI：
10.1016/j.immuni.2008.11.011
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发表时间：
2009-02-20
期刊：
影响因子：
32.4
通讯作者：
Rossjohn, Jamie
中科院分区：
文献类型：
--
作者：
Gras, Stephanie;Burrows, Scott R.;Rossjohn, Jamie
在选择 T 细胞库的过程中，免疫系统会区分自我限制和自我耐受之间的微妙区别，但如何实现这一点尚不清楚。在这里，我们描述了对atrans-HLA（人类白细胞抗原）同种异型的自我耐受如何影响T细胞受体（TCR）对EB病毒（EBV）决定簇（FLRGRAYGL）的识别。比较了两种原型 TCR 对 HLA-B8-FLRGRAYGL 的识别。一种是公开选择的TCR，LC13，与HLA-B44有同种异体反应；另一种是 CF34，缺乏 HLA-B44 反应性，因为它是在 HLA-B44 与 HLA-B8 反式共同遗传时产生的。同种异体反应性 LC13 TCR 对接在 HLA-B8-FLRGRAYGL 的 C 末端，而 CF34 TCR 对接在 HLA-B8-FLRGRAYGL 的 N 末端，这与 HLA-B8 和 HLA-B44 之间的多态性区域一致。 LC13 和 CF34 TCR 的显着对比足迹描绘了自我耐受如何塑造被选入免疫库的 TCR 的特异性。
During selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward atrans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire.