Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease
Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease
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DOI：
10.1038/10563
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发表时间：
1999-07-01
期刊：
影响因子：
82.9
通讯作者：
Goulmy, E
中科院分区：
文献类型：
--
作者：
Mutis, T;Gillespie, G;Goulmy, E
移植物抗宿主病（GvHD）是异基因骨髓移植的主要并发症（1）。在HLA相合的骨髓移植中，GvHD可能是由供体和受体之间的次要组织相容性抗原（mHags）的差异引起的，抗原存在于受体中而不在供体中（2）。可以从患有严重GvHD的受体的血液中分离对受体的mHags具有特异性的细胞毒性T淋巴细胞（CTL）（参考文献3）。一项回顾性研究表明，在来自HLA基因型相同供体的骨髓成人受者中，mHags HA-1、-2、-4和-5的错配与GvHD的发生之间存在相关性（4）。四聚体HLA-肽复合物已用于在HIV感染个体中以及在EB病毒和淋巴细胞性脉络丛脑膜炎病毒感染期间可视化和定量抗原特异性CTL（5-8）。在这里，我们显示了在GvHD期间使用四聚体HLA类和1-mHag HA-1和HY肽复合物的mHag特异性CTL的直接离体可视化。在17例HA-1或HY错配的骨髓受体中，早在骨髓移植后14天就检测到HA-1和MY特异性CTL。在急性和慢性GvHD过程中，四聚体复合物显示HA-1和MY特异性CTL显著增加，而在成功的GvHD治疗后则减少。HLA 1类-mHag肽四聚体可作为临床诊断和监测GvHD患者的工具。
Graft-versus-host disease (GvHD) is a chief complication of allogeneic bone marrow transplantation(1). In HLA-identical bone marrow transplantation, GvHD may be induced by disparities in minor histocompatibility antigens (mHags) between the donor and the recipient, with the antigen being present in the recipient and not in the donort(2). Cytotoxic T lymphocytes (CTLs) specific for mHags of the recipients can be isolated from the blood of recipients with severe GvHD (ref. 3). A retrospective study demonstrated an association between mismatch for mHags HA-1, -2, -4 and -5 and the occurrence of GvHD in adult recipients of bone marrow from HLA genotypically identical donors(4). Tetrameric HLA-peptide complexes have been used to visualize and quantitate antigen-specific CTLs in HIV-infected individuals and during Epstein-Barr virus and lymphocytic choriomeningitis virus infections(5-8). Here we show the direct ex vivo visualization of mHag-specific CTLs during GvHD using tetrameric HLA-class and 1-mHag HA-1 and HY peptide complexes. In the peripheral blood of 17 HA-1 or HY mismatched marrow recipients, HA-1-and MY-specific CTLs were detected as early as 14 days after bone marrow transplantation. The tetrameric complexes demonstrated a significant increase in HA-1- and MY-specific CTLs during acute and chronic GvHD, which decreased after successful GvHD treatment. HLA class 1-mHag peptide tetramers may serve as clinical tools for the diagnosis and monitoring of GvHD patients.