Funktionelle Analyse der Proteasomregulatoren PI31, PA28y/Ki und warum PA28aß die Generierung von MHC Klasse I Epitopen unterstützt Functional analysis of proteasome regulators PI31, PA28y/Ki and why the PA28aß supports the generation of MHC class I antig

PA28g或ki自身抗原，细胞蛋白酶体抑制剂PI31和DPa28b亚基是最有可能参与蛋白酶体活性调节的蛋白质。虽然它们的体外活性被很好地表征，但它们在体内的功能几乎一无所知。基于生成的生化和分子数据，我们将重点分析这些蛋白质的体内功能。在这里，我们将特别关注它们在蛋白酶体依赖性MHC I类抗原呈递不同病毒蛋白中的潜在作用。为此，我们将分析ki敲除小鼠，并建立在Tet调控启动子控制下表达这些蛋白的转染细胞系。PI31， PA28g和DPA28b对抑制或激活抗原呈递的作用将通过肽特异性细胞毒性T细胞测定来监测。将研究观察到的效应的分子和细胞原因。

PA28g or the Ki-auto-antigen, the cellular proteasome inhibitor PI31 and the DPa28b subunits are proteins which most likely are involved in the modulation of proteasome activity. While their in vitro activities are well characterised almost nothing is known about their in vivo function(s). Based on the biochemical and molecular data generated we therefore will focus on the analysis of the in vivo function of these proteins. Here we will in particular concentrate on their potential role in proteasome dependent MHC class I antigen presentation of different viral proteins. With this aim we will analyse Ki-knock out mice and will established transfected cell line which express these protein under the control of a Tet regulated promoter. The effect of PI31, PA28g and DPA28b on inhibition or activation of antigen presentation will be monitored by peptide specific cytotoxic T cell assays. The molecular and cellular reasons for observed effects will be investigated.