Intragraft Selection of the T Cell Receptor Repertoire by Class I MHC Sequences in Tolerant Recipients
Intragraft Selection of the T Cell Receptor Repertoire by Class I MHC Sequences in Tolerant Recipients
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DOI：
10.1371/journal.pone.0006076
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发表时间：
2009-06-29
期刊：
影响因子：
3.7
通讯作者：
Ghobrial, Rafik M.
中科院分区：
文献类型：
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作者：
Liu, Dahai;Shen, Xiu-Da;Ghobrial, Rafik M.
背景：急性心肌梗死(RT1(A))受体对WF(RT1(U))心脏的同种异体移植耐受可由受体类型(RT1A(A))序列上显示的供体型(RT1A(U))免疫原性表位的同种嵌合I类MHC分子诱导。在这里，我们试图通过T细胞受体(TCA)谱系限制同种异基因序列影响应答T细胞的机制。方法/主要发现：在亚治疗剂量环孢素(CsA)存在的情况下，可溶性[α(U)(1h)]-RT1.A(A)异基因分子被输送到WF心脏的ACI受者体内。移植后+5天和+7天，同种异体大剂量环孢素A耐受受者的T细胞受体Vβ基因家族在TCR谱系中有差异表达。然而，在移植后第30天，异基因嵌合分子处理的大鼠表现出TCR谱带的限制，显性大小的峰改变，代表Vβ7、Vβ11、Vβ13、Vβ14和Vβ15基因的优先克隆性扩展。结论：部分模拟供者和受者表位的同种异体MHC-I类序列的出现可能通过选择同种异体反应的Vβ基因来诱导独特的耐受状态。
Background: Allograft tolerance of ACI (RT1(a)) recipients to WF (RT1(u)) hearts can be induced by allochimeric class I MHC molecules containing donor-type (RT1A(u)) immunogenic epitopes displayed on recipient-type (RT1A(a)) sequences. Here, we sought the mechanisms by which allochimeric sequences may affect responding T cells through T cell receptor (TCA) repertoire restriction.Methodology/Principal Findings: The soluble [alpha(u)(1h)]-RT1.A(a) allochimeric molecule was delivered into ACI recipients of WF hearts in the presence of sub-therapeutic dose of cyclosporine (CsA). The TCR V beta spectrotyping of the splenocytes and cardiac allografts showed that the V beta gene families were differentially expressed within the TCR repertoire in allochimericor high-dose CsA-treated tolerant recipients at day + 5 and + 7 of post-transplantation. However, at day 30 of post-transplantation the allochimeric molecule-treated rats showed the restriction of TCR repertoire with altered dominant size peaks representing preferential clonal expansion of V beta 7, V beta 11, V beta 13, V beta 14, and V beta 15 genes. Moreover, we found a positive correlation between the alteration of Vb profile, restriction of TCR repertoire, and the establishment of allograft tolerance.Conclusions: Our findings indicate that presentation of allochimeric MHC class I sequences that partially mimic donor and recipient epitopes may induce unique tolerant state by selecting alloresponsive V beta genes.