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正常和恶性来源的人B细胞系上HLA抗原的差异表达:是免疫监视的结果还是祖细胞的表型遗迹?

Differential expression of HLA antigens on human B-cell lines of normal and malignant origin: a consequence of immune surveillance or a phenotypic vestige of the progenitor cells?

作者信息

Torsteinsdottir S, Brautbar C, Klein G, Klein E, Masucci M G

机构信息

Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.

出版信息

Int J Cancer. 1988 Jun 15;41(6):913-9. doi: 10.1002/ijc.2910410625.

Abstract

Pairs of BL-derived cell lines and in vitro EBV-transformed LCLs, derived from the same patient, were compared for the expression of MHC class-I antigenic determinants as shown both by monoclonal antibody (MAb) binding and by sensitivity to HLA-specific CTL clones. BL lines expressed all polymorphic determinants tested at a lower level than the corresponding LCLs, as indicated by the binding of the MAbs AUF 5.13 (anti-HLA A3,A11), GS 142.1 (anti-HLA A1), GS 114.1 (anti-HLA A24), GSP 35.1 (anti-HLA A2,A28), GSP 55.1 (anti-HLA A25,A32), TER MA32 (anti-HLA A32), GSP 145.2 (anti-HLA B27), B27 M.1 (anti-HLA B27,B7) and GSP 8.1 (anti-HLA B8). The difference was most pronounced for HLA A11 and least for B27,A1 and B8 with intermediate differences for the other specificities. The BL lines were also less sensitive to lysis by HLA-specific CTL clones directed to the same and to additional antigens. The polymorphic determinants detected by the AUF 5.13 and GSP 35.1. MAbs were expressed at a lower level in resting T and B cells compared to mitogen- and EBV-induced blasts. An analogous change in the expression of polymorphic determinants was observed in EBV-converted sublines of originally EBV-negative BLs that have become more "LCL-like" after conversion. The appearance of B-cell activation markers was paralleled by the up-regulation of both the serologically defined and the CTL-target epitopes. The findings suggest that the low expression of HLA determinants on the BL cells is a phenotypic vestige of the normal BL precursor.

摘要

对源自同一患者的成对的伯基特淋巴瘤(BL)衍生细胞系和体外爱泼斯坦-巴尔病毒(EBV)转化的淋巴母细胞系(LCL),就主要组织相容性复合体(MHC)I类抗原决定簇的表达进行了比较,比较方式包括单克隆抗体(MAb)结合以及对HLA特异性细胞毒性T淋巴细胞(CTL)克隆的敏感性。如MAb AUF 5.13(抗HLA A3、A11)、GS 142.1(抗HLA A1)、GS 114.1(抗HLA A24)、GSP 35.1(抗HLA A2、A28)、GSP 55.1(抗HLA A25、A32)、TER MA32(抗HLA A32)、GSP 145.2(抗HLA B27)、B27 M.1(抗HLA B27、B7)和GSP 8.1(抗HLA B8)的结合所示,BL细胞系表达的所有测试多态性决定簇水平均低于相应的LCL。对于HLA A11,差异最为显著;对于B27、A1和B8,差异最小;对于其他特异性,差异处于中间水平。BL细胞系对针对相同及其他抗原的HLA特异性CTL克隆的裂解也较不敏感。与有丝分裂原和EBV诱导的母细胞相比,AUF 5.13和GSP 35.1 MAb检测到的多态性决定簇在静止T细胞和B细胞中的表达水平较低。在最初EBV阴性的BL的EBV转化亚系中观察到多态性决定簇表达的类似变化,这些亚系在转化后变得更“LCL样”。B细胞活化标志物的出现与血清学定义的表位和CTL靶表位的上调同时发生。这些发现表明,BL细胞上HLA决定簇的低表达是正常BL前体细胞的表型遗迹。

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