Landis Eric D, Palti Yniv, Dekoning Jenefer, Drew Robert, Phillips Ruth B, Hansen John D
Molecular Medicine Program, University of Maryland Medical School, Baltimore, Maryland, USA.
Immunogenetics. 2006 Feb;58(1):56-69. doi: 10.1007/s00251-005-0070-5. Epub 2006 Jan 27.
Tapasin (TAPBP) is a key member of MHC class Ia antigen-loading complexes, bridging the class Ia molecule to the transporter associated with antigen presentation (TAP). As part of an ongoing study of MHC genomics in rainbow trout, we have identified two rainbow trout TAPBP genes (Onmy-TAPBP.a and .b) and a similar but distinct TAPBP-related gene (Onmy-TAPBP-R) that had previously only been described in mammals. Physical and genetic mapping indicate that Onmy-TAPBP.a is on chromosome 18 in the MHC class Ia region and that Onmy-TAPBP.b resides on chromosome 14 in the MHC class Ib region. There are also at least two copies of TAPBP-R, Onmy-TAPBP-R.a and Onmy-TAPBP-R.b, located on chromosomes 2 and 3, respectively. Due to the central role of TAPBP expression during acute viral infection, we have characterized the transcriptional profile and regulatory regions for both Onmy-TAPBP and Onmy-TAPBP-R. Transcription of both genes increased during acute infection with infectious hematapoeitic necrosis virus (IHNV) in a fashion indicative of interferon-mediated regulation. Promoter-reporter assays in STE-137 cells demonstrate that the trout TAPBP and TAPBP-R promoters respond to interferon regulatory factors, Onmy-IRF1 and Onmy-IRF2. Overall, TAPBP is expressed at higher levels than TAPBP-R in naïve tissues and TAPBP transcription is more responsive to viral infection and IRF1 and 2 binding.
塔帕辛(TAPBP)是MHC I类a型抗原加载复合物的关键成员,它将I类a型分子与抗原呈递相关转运体(TAP)连接起来。作为对虹鳟MHC基因组学正在进行的研究的一部分,我们鉴定出了两个虹鳟TAPBP基因(Onmy-TAPBP.a和.b)以及一个类似但不同的TAPBP相关基因(Onmy-TAPBP-R),该基因此前仅在哺乳动物中被描述过。物理和遗传图谱分析表明,Onmy-TAPBP.a位于MHC I类a型区域的18号染色体上,Onmy-TAPBP.b位于MHC I类b型区域的14号染色体上。TAPBP-R也至少有两个拷贝,即Onmy-TAPBP-R.a和Onmy-TAPBP-R.b,分别位于2号和3号染色体上。由于TAPBP表达在急性病毒感染过程中发挥核心作用,我们对Onmy-TAPBP和Onmy-TAPBP-R的转录谱及调控区域进行了特征分析。在感染传染性造血器官坏死病毒(IHNV)的急性感染期间,这两个基因的转录均增加,其方式表明是由干扰素介导的调控。在STE-137细胞中进行的启动子-报告基因检测表明,虹鳟TAPBP和TAPBP-R启动子对干扰素调节因子Onmy-IRF1和Onmy-IRF2有反应。总体而言,在未感染的组织中,TAPBP的表达水平高于TAPBP-R,并且TAPBP转录对病毒感染以及IRF1和2的结合更敏感。