In vivo expansion of HLA-B35 alloreactive T cells sharing homologous T cell receptors: evidence for maintenance of an oligoclonally dominated allospecificity by persistent stimulation with an autologous MHC/peptide complex

In vivo expansion of HLA-B35 alloreactive T cells sharing homologous T cell receptors: evidence for maintenance of an oligoclonally dominated allospecificity by persistent stimulation with an autologous MHC/peptide complex
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共享同源 T 细胞受体的 HLA-B35 同种反应性 T 细胞的体内扩增:通过自体 MHC/肽复合物持续刺激维持寡克隆主导的同种异体特异性的证据

DOI:
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发表时间:
1995
影响因子:
15.3
通讯作者:
Dolores J. Schendel
Dolores J. Schendel
中科院分区:
医学1区
文献类型:
--
作者:
Alexander Steinle;Carsten Reinhardt;Petra Jantzer;Dolores J. Schendel

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由T淋巴细胞看到的同种异体抗原的性质,特别是肽在同种异体识别中的作用,已经被深入研究,而关于同种异体反应性T细胞的体内出现、多样性和特异性的结构基础的知识非常有限。在这里,我们描述了人类T细胞克隆识别HLA-B35同种抗原的肽依赖性的方式。TCR序列分析显示,这些同种异体特异性克隆中的几个利用同源TCR:它们都表达具有高度相关的CDR 3序列的TCRBV 2S 3 J36 C1和TCRBV 4S 1 J2 S7 C2链。因此,肽特异性同种异体反应性以类似于识别标称肽/自身MHC复合物的T细胞所述的方式反映在同源CDR 3序列中。该TCR特异性的体内频率在未受刺激的应答细胞供体的PBL中进行研究,所述应答细胞供体未对HLA-B35致敏。绝大多数(约75%)的VA 2S 3 J36交界区从两个样本的PBL,分离在9年的时间间隔,编码的CDR 3相同或同源的功能特征的HLA-B35同种异体特异性T细胞。这些数据是最容易解释的同种异体反应性的模型,其中持续或反复暴露于外源肽/自身-MHC复合物导致体内扩增和长期维持的特定T细胞,显示偶然的交叉识别的HLA-B35/肽复合物和占主导地位的同种异体反应对HLA-B35。
The nature of alloantigens seen by T lymphocytes, in particular the role of peptides in allorecognition, has been studied intensively whereas knowledge about the in vivo emergence, diversity, and the structural basis of specificity of alloreactive T cells is very limited. Here we describe human T cell clones that recognize HLA-B35 alloantigens in a peptide-dependent manner. TCR sequence analysis revealed that several of these allospecific clones utilize homologous TCR: they all express TCRAV2S3J36C1 and TCRBV4S1J2S7C2 chains with highly related CDR3 sequences. Thus peptide-specific alloreactivity is reflected in homologous CDR3 sequences in a manner similar to that described for T cells that recognize nominal peptide/self-MHC complexes. The in vivo frequency of this TCR specificity was studied in unstimulated PBL of the responding cell donor who was not sensitized against HLA-B35. The vast majority (approximately 75%) of the VA2S3J36 junctional regions obtained from two samples of PBL, isolated at a 9-yr interval, encode CDR3 identical or homologous to those of the functionally characterized HLA-B35 allospecific T cells. These data are most easily explained by a model of alloreactivity in which persistent or recurrent exposure to a foreign peptide/self-MHC complex led to the in vivo expansion and long-term maintenance of specific T cells that show fortuitous crossrecognition of an HLA-B35/peptide complex and dominate the alloresponse against HLA-B35.
DOI: 10.1126/science.1546328
发表时间: 1992-03-06
期刊: SCIENCE
影响因子: 56.9
作者:
HUNT, DF;HENDERSON, RA;ENGELHARD, VH
通讯作者: ENGELHARD, VH
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DOI: --
发表时间: 1989
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Shimizu,Y;DeMars,R
通讯作者: DeMars,R
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DOI: --
发表时间: 1989
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Miceli,MC;Finn,OJ
通讯作者: Finn,OJ
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DOI: --
发表时间: 1991
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Geiger,MJ;Gorski,J;Eckels,DD
通讯作者: Eckels,DD