Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone.
Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone.
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由同种异体反应性 T 淋巴细胞克隆识别的自身 MHC 限制性肽。
DOI：
10.4049/jimmunol.157.2.670
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发表时间：
1996
影响因子：
4.4
通讯作者：
Peter Walden
中科院分区：
文献类型：
--
作者：
Keiko Udaka;K. Wiesmüller;S. Kienle;Günther Jung;Peter Walden
同种异体反应性T淋巴细胞在未致敏的动物中很容易检测到，尽管它们以前从未遇到过同种异体抗原。这种公认的现象通常用这样的假设来解释，即与确定的肽复合的自身MHC分子类似于具有另一种肽的同种MHC分子，并诱导相应的T细胞特异性。在这里，第一次和支持这一假设，自我MHC限制性肽描述的T细胞克隆，诱导与异源MHC。同种异体MHC特异性CTL克隆2C来自H-2b小鼠，并识别与天然存在的内源性肽LSPFPFDL复合的H-2Ld。H-2Kb被证明参与其TCR的阳性选择，与该MHC分子相关的肽参与该过程。为了鉴定此类肽，采用随机肽库的位置扫描结合迭代方法。发现了几种活性肽，并选择最有效的SIYRYYGL进行进一步研究。2C对两种MHC-肽加合物H-2Ld + LSPFPFDL和H-2Kb + SIYRYYGL的识别是由相同的TCR介导的，并且似乎与从使用Id特异性Ab的抑制实验得出的结论类似地有效。来自SIYRYYGL致敏的H-2b小鼠的CTL对H-2Ld + LSPFPFDL应答。这种相互交叉反应性表明两种MHC-肽复合物共享结构特征。
Alloreactive T lymphocytes are readily detected in unprimed animals although they have never encountered the alloantigen before. This well-established phenomenon is usually explained with the assumption that a self-MHC molecule complexed with a defined peptide resembles the allo-MHC molecule with another peptide and induces the corresponding T cell specificities. Here, for the first time and in support of this hypothesis, self-MHC-restricted peptides are described for a T cell clone that was induced with allo-MHC. The allo-MHC-specific CTL clone 2C was derived from a H-2b mouse and recognizes H-2Ld complexed with the naturally occurring endogenous peptide LSPFPFDL. H-2Kb was shown to be involved in positive selection of its TCR, and peptides associated with this MHC molecule are implicated in the process. To identify such peptides, positional scanning with random peptide libraries combined with an iterative approach was employed. Several active peptides were found and the most efficient, SIYRYYGL, was chosen for further studies. Recognition by 2C of the two MHC-peptide adducts H-2Ld + LSPFPFDL and H-2Kb + SIYRYYGL is mediated by the same TCR and appears to be similarly efficient as concluded from inhibition experiments with an Id-specific Ab. CTLs from SIYRYYGL-primed H-2b mice respond to H-2Ld + LSPFPFDL. This reciprocal cross-reactivity suggests that structural features are shared by the two MHC-peptide complexes.