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

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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.