Modulation of T cell development by an endogenous altered peptide ligand.
Modulation of T cell development by an endogenous altered peptide ligand.
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DOI：
10.1084/jem.181.2.805
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发表时间：
1995-02-01
期刊：
影响因子：
--
通讯作者：
Allen PM
中科院分区：
文献类型：
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作者：
Hsu BL;Evavold BD;Allen PM
T细胞在胸腺和周围的选择过程中可能遇到许多内源性肽。我们研究了内源性肽对体内T细胞发育的影响，使用基于血红蛋白特异性T细胞克隆的TCR转基因小鼠模型。在这些小鼠中，转基因β链与内源性α链配对。这导致了对亲本克隆Hbd（64-76）表位改变的肽配体Ser69肽的偶然初级反应。鉴定出两个ser69反应性T细胞群。一小部分Ser69反应性T细胞对Ser69和Hbd都有反应（64-76）。大多数只对Ser69反应，对Hbd不反应（64-76）；事实上，Hbd（64-76）是这些仅ser69反应性T细胞的特异性TCR拮抗剂。因此，在这个独特的实验系统中，Ser69成为激动剂，而Hbd（64-76）是拮抗剂。内源性拮抗剂配体在胸腺中的呈递选择性地消除了高亲和性细胞，同时保留了ser69反应性T细胞库中的低亲和性细胞。这些结果强调了特异性如何通过配体网络引导发育中的T细胞，并表明内源性肽库对T细胞的发育和库具有深远的影响。
T cells potentially encounter numerous endogenous peptides during selection in the thymus and in the periphery. We examined the impact of an endogenous peptide on in vivo T cell development, using a TCR transgenic mouse model based on a hemoglobin-specific T cell clone. In these mice, the transgenic beta chains paired with endogenous alpha chains. This led to a serendipitous primary reactivity to Ser69 peptide, an altered peptide ligand of the Hbd (64-76) epitope of the parent clone. Two Ser69-reactive T cell populations were identified. A smaller population of the Ser69-reactive T cells responded both to Ser69 and Hbd (64-76). A majority reacted only to Ser69, and not to Hbd(64-76); in fact, Hbd(64-76) was a specific TCR antagonist for these Ser69-only-reactive T cells. Thus, in this unique experimental system, Ser69 became an agonist, and Hbd (64-76) was an antagonist. Endogenous presentation of the antagonist ligand in the thymus selectively eliminated the high-avidity cells, while sparing low-avidity cells in the Ser69-reactive T cell repertoire. These results highlight how specificity guides developing T cells through a network of ligands and indicate that the endogenous peptide pool has a profound effect on T cell development and repertoire.