Identification of HLA class II-restricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Y-mismatched transplantation
Identification of HLA class II-restricted H-Y-specific T-helper epitope evoking CD4+ T-helper cells in H-Y-mismatched transplantation
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DOI：
10.1016/s0140-6736(03)14191-8
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发表时间：
2003-08-23
期刊：
影响因子：
168.9
通讯作者：
Goulmy, E
中科院分区：
文献类型：
--
作者：
Spierings, E;Vermeulen, CJ;Goulmy, E
当存在性别不匹配时，hla相同的兄弟姐妹之间的干细胞移植不太可能成功。这种缺乏成功可以解释为针对Y染色体编码的次要组织相容性抗原（H-Y）的活性增强。到目前为止，在人类中，仅报道了几种次要组织相容性抗原特异性的细胞毒性T淋巴细胞（ctl）。我们的目的是确定和阐明MHC ii类限制性h - y特异性t辅助细胞在这些移植环境中的作用。方法从排斥hla -同型男性干细胞移植的女性患者血液中分离h - y特异性MHC ii类限制性CD4+ T细胞。通过H-Y基因的分子克隆和功能性t辅助细胞实验，我们阐明了这些H-Y特异性t辅助细胞的抗原特异性和功能特性。结果CD4+ t辅助细胞可识别HLA-DRbeta3*0301呈递的Y基因编码肽VIKVNDTVQI。这些t辅助细胞使树突状细胞成熟，并增强次要组织相容性抗原特异性MHC i类限制性CD8+ ctl的扩增。诱导CD4+ t辅助应答的MHC ii类限制性H-Y表位的特征为针对Y染色体编码的次要组织相容性抗原的同种免疫应答增加了一种新的细胞成分。这一成分完成了h - y导向的同种免疫反应，并有助于理解性别错配移植的不良结果。
Background Stem-cell grafts between HLA-identical siblings are less likely to succeed when there is a sex mismatch. This lack of success can be interpreted as enhanced activity directed against minor histocompatibility antigens encoded by the Y chromosome (H-Y). So far, in man, only cytotoxic T lymphocytes (CTLs) specific for several minor histocompatibility antigens have been reported. We aimed to identify and clarify the role of MHC class II-restricted H-Y-specific T-helper cells in these transplant settings.Methods H-Y-specific MHC class II-restricted CD4+ T cells were isolated from blood of a female patient who rejected an HLA-identical male stem-cell transplant. By molecular cloning of H-Y genes and functional T-helper experiments, we elucidated antigen specificity and the functional properties of these H-Y-specific T-helper cells.Findings CD4+ T-helper cells recognise the Y gene-encoded peptide VIKVNDTVQI presented by HLA-DRbeta3*0301. These T-helper cells mature dendritic cells and enhance expansion of minor histocompatibility antigen-specific MHC class I-restricted CD8+ CTLs.Interpretation Characterisation of an MHC class II-restricted H-Y epitope that evoked CD4+ T-helper responses adds a novel cellular component to the alloimmune response against Y chromosome-encoded minor histocompatibility antigens. This component completes the H-Y-directed alloimmune response and aids understanding of the poorer outcome of sex-mismatched transplants.