Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expression and their Upregulation by IFN‐γ
Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expression and their Upregulation by IFN‐γ
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人胚胎癌中 MHC I 类抗原呈递机制的分析：TAP、LMP 和 MHC I 类表达缺陷及其被 IFN-γ 上调的证据
DOI：
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发表时间：
1997
影响因子：
3.7
通讯作者：
H. Schmoll
中科院分区：
文献类型：
--
作者：
B. Seliger;T. Dunn;T. Dunn;A. Schwenzer;Jochen Casper;C. Huber;H. Schmoll;H. Schmoll
主要组织相容性复合体I类抗原在植入后早期胚胎细胞和胚胎癌细胞中的表达受到抑制，但经干扰素-γ或维甲酸处理后表达上调。在许多人类和小鼠肿瘤中，MHC-I类抗原处理机制的不同组成部分的表达缺陷，如蛋白酶体亚单位LMP-2和LMP-7以及肽转运体TAP-1和TAP-2，是MHC I类表面表达受损的原因。在这里，我们分析了人EC细胞系577LM中LMP、TAP和MHC-I类分子的组成和干扰素-γ调节的基因和蛋白的表达。与淋巴母细胞对照细胞相比，577LM细胞中LMP-7、TAP-1、HLAI和β-2微球蛋白的表达较低，而TAP-2和LMP-2的表达不明显。无论是低温培养细胞还是与外源性MHC-I类结合多肽共同孵育都不能增强577LM细胞表面MHC-I类分子的表达，因此，MHC-I类分子的表达缺陷不仅是由于抗原肽的生成和加工障碍所致。干扰素-γ处理577Lm后，MHC-I类蛋白表达显著增加，TAP、LMP、MHC-I类转录及TAP-1、TAP-2蛋白表达上调，而LMP-2、LMP-7蛋白表达无明显变化。这些数据表明，人EC细胞株稳定表达MHC I类低/缺陷表型。与这种表型相关的缺陷涉及不同水平的MHC-I类限制性抗原呈递机制，并可以通过干扰素-γ治疗而得到改善。
The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post‐implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)‐γ or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP‐2 and LMP‐7 and the peptide transporters TAP‐1 and TAP‐2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN‐γ regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human EC line 577LM. In comparison to lymphoblastoid control cells, poor constitutive mRNA and protein expression of LMP‐7, TAP‐1, HLA class I, and β2‐microglobulin, but not of TAP‐2 and LMP‐2, was detected in 577LM cells. The lack of MHC class I surface expression on 577LM cells could not be enhanced either by culturing cells at low temperature or by their incubation with exogenous MHC class I specific binding peptides: thus, the defective MHC class I surface expression was not only caused by impaired generation and processing of antigenic peptides. IFN‐γ treatment of 577LM resulted in a significant increase of MHC class I surface expression which was preceded by an upregulation of TAP, LMP and MHC class I transcripts as well as of TAP‐1 and TAP‐2, but not of LMP‐2 and LMP‐7, protein expression. These data suggest that human EC cell lines show a stable expression of a MHC class I low/deficient phenotype. The deficiencies associated with this phenotype involve different levels of the MHC class I restricted antigen presentation machinery and could be modified by treatment with IFN‐γ.
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从体节期小鼠胚胎建立细胞系并在这些细胞中表达主要组织相容性 I 类基因。
DOI：
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发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Silverman,T;Rein,A;Orrison,B;Langloss,J;Bratthauer,G;Miyazaki,J;Ozato,K
通讯作者：
Ozato,K
DOI：
10.1016/s0167-5699(97)80026-6
发表时间：
1997-06
期刊：
Immunology today
影响因子：
--
作者：
Barbara Seliger;Barbara Seliger;Markus Maeurer;Markus Maeurer;Soldano Ferrone;Soldano Ferrone
通讯作者：
Barbara Seliger;Barbara Seliger;Markus Maeurer;Markus Maeurer;Soldano Ferrone;Soldano Ferrone
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影响因子：
11.2
作者：
Wang,Z;Hu,XZ;Tatake,RJ;Yang,SY;Zeff,RA;Ferrone,S
通讯作者：
Ferrone,S
人畸胎癌衍生细胞系 MHC 抗原的表达。
影响因子：
--
作者：
Andrews,PW;Bronson,DL;Wiles,MV;Goodfellow,PN
通讯作者：
Goodfellow,PN
畸胎癌细胞 MHC 抗原表达在体外受可溶性非干扰素因子调节。
影响因子：
4.3
作者：
Ostrand-Rosenberg,S;Schwartzman,ML;Hecht,TT;Marr,L
通讯作者：
Marr,L