Impact of the proteasomal immune adaptation on the early immune response to viral infection

• Applicant: Professorin Dr. Elke Beate Krüger
• Subject Area: Immunology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40649020

Peptide generation by the proteasome is rate limiting in major histocompatibility complex (MHC) class I restricted antigen presentation in response to virus induced Interferons (IFN). IFN-mediated de novo formation of immunoproteasomes (i20S) therefore essentially supports the rapid adjustment of the mammalian immune system to pathogens. This adjustment is of particular importance for the immune response to rapidly replicating viruses. Recently, we have shown that i20S formation is an accelerated and transient response. Moreover, we demonstrated that i20S and/or PA28 are essentially required for the generation of certain viral epitopes. The main focus of the proposed research program is the detailed investigation of early stages of the induction of 20S formation and the resulting MHC class I immune response within the first 24 hours after an immunological challenge (type I and II IFNs, polyl:C, CpG oligonucleotides, virus infection models). The overall concept includes the characterization of the induction kinetics of the de novo formed 20S complexes and their interaction with regulatory complexes as the 19S regulator or PA28α/β. In addition to i20S and constitutive 20S, we also expect the formation of functionally active mixed-type 20S proteasomes (m20S) containing both immuno- as well as constitutive subunits. We shall analyze the composition of the resulting proteasome complexes at these early time points and their impact on MHC class I antigen presentation by different immunological read out systems.

• DFG Programme: Research Grants
• Participating Person: Professorin Dr. Ulrike Seifert