Discoordinate surface expression of IFN-gamma-induced HLA class II proteins in nonprofessional antigen-presenting cells with absence of DM and class II colocalization.
Discoordinate surface expression of IFN-gamma-induced HLA class II proteins in nonprofessional antigen-presenting cells with absence of DM and class II colocalization.
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DOI：
10.4049/jimmunol.160.7.3207
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发表时间：
1998-04
影响因子：
4.4
通讯作者：
K. Muczynski;S. Anderson;D. Pious
中科院分区：
文献类型：
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作者：
K. Muczynski;S. Anderson;D. Pious
我们比较了人类黑色素瘤细胞系(非专业性APC)和EBV转化的B淋巴母细胞系(专业性APC)在干扰素-γ诱导或稳定转染CIITA后的HLAII类表达。干扰素-γ诱导和CIITA转基因黑色素瘤细胞表达DR、DP和DQ的水平与专业APC的表达水平相似，但在干扰素-γ诱导下，DP、DQ蛋白和DM依赖的DR表位延迟出现在细胞表面。尽管Northern blotting显示II类基因和DM基因协同转录，并且它们的mRNA水平与B淋巴母细胞相同，但仍观察到一些由干扰素-γ诱导的II类表位在细胞表面的延迟表达。共聚焦显微镜显示，与专业APC相比，在黑色素瘤细胞系中，由于干扰素-γ诱导的II类蛋白在细胞内的转运不同，导致了细胞表面II类蛋白的不协调表达。具体地说，虽然DR和DM蛋白在干扰素-γ诱导后2天就存在，但在诱导后的任何时间，DR和DM蛋白在细胞内的共存并不明显。DR和DM蛋白不能共定位表明，干扰素-γ诱导的细胞缺乏细胞内类似MIIC的隔室。缺乏含有DR和DM的隔间以促进两种蛋白质之间的相互作用，可能是II类表位延迟表面表达的原因，其形成既需要II类又需要DM。
We compared HLA class II expression in a human melanoma line (a nonprofessional APC), induced by IFN-gamma or by stable transfection with CIITA, with constitutive class II expression in an EBV-transformed B lymphoblastoid cell line (a professional APC) from the same donor. IFN-gamma-induced and CIITA-transfected melanoma cells expressed DR, DP, and DQ at levels similar to those expressed by the professional APC; however, DP and DQ proteins and DM-dependent DR epitopes were delayed in appearing on the cell surface when induced by IFN-gamma. The delay in cell surface expression of some IFN-gamma-induced class II epitopes was observed even though Northern blots demonstrated class II and DM genes to be coordinately transcribed and their mRNA levels to be equivalent to that in B lymphoblastoid cells. Confocal microscopy suggests that discoordinate cell surface expression of class II results from different intracellular trafficking for IFN-gamma-induced class II proteins in the melanoma line compared with that in professional APCs. Specifically, although DR and DM proteins were present 2 days after IFN-gamma induction, colocalization of DR and DM proteins intracellularly was not apparent in cells at any time after induction. Failure of DR and DM proteins to colocalize suggests that IFN-gamma-induced cells lack an intracellular MIIC-like compartment. The absence of a compartment containing DR and DM to facilitate interaction between the two proteins may account for the delayed surface expression of class II epitopes whose formation requires both class II and DM.