Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level.
Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level.
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DOI：
10.1084/jem.150.6.1310
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发表时间：
1979-12-01
期刊：
影响因子：
--
通讯作者：
Fellous M
中科院分区：
文献类型：
--
作者：
Lipinski M;Fridman WH;Tursz T;Vincent C;Pious D;Fellous M
来自传染性单核细胞增多症（IM）患者的外周T淋巴细胞在体内针对EB病毒（EBV）致敏。靶细胞表面HLA-A、B或C分子的表达对于细胞毒性反应是必需的，因为（a）缺乏HLA-A、B和C决定簇的EBV阳性Daudi细胞对抗EBV T细胞裂解具有抗性，（B）EBV阳性靶细胞的细胞裂解可以被抗HLA-A、B和C以及抗β 2微球蛋白抗体持续抑制。然而，在该系统中没有明显的同种异体限制的证据，因为（a）来自一个给定个体的细胞毒性T淋巴细胞（CTL）可以对不同的EBV阳性靶细胞发挥相似程度的细胞毒性，而不管效应物和靶所共有的HLA-A或B特异性的数量;（B）来自IM患者的CTL能够杀死靶细胞，而没有任何共同的HLA-A或B抗原;和（c）在A、B或D基因座缺少一种或两种HLA抗原的T5-1变体被杀死至与亲本细胞相同的程度。在9例可检测到循环抗EBV CTL的IM患者中，7例携带HLA-A1抗原，而在16例缺乏可检测到的外周CTL的IM患者中，无一例为HLA-A1阳性（来自HLA-A1阳性患者的T细胞对T5-1靶细胞的平均特异性裂解：29.3%对HLA-A1阴性患者的0.6%）（P <10（-9））。这些数据表明HLA-A1连锁的基因控制抗EBV CTL应答的大小。因此，HLA区域似乎在两个不同的水平上作用于T细胞介导的EBV感染细胞的裂解，首先控制抗EBV的产生，其次控制作为靶细胞表面识别结构的HLA-A、B和C分子的表达。
Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T- cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA- A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti- EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti- EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface.