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Universität Bonn
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Research interests

Research Unit Prof. Dr. Norbert Koch

Head of Research UnitNorbert Koch
Prof. Dr. Norbert Koch
Immunbiology Unit

Phone: 0228-73-4343
Fax: 0228-73-4263
 

 

  

 

Curriculum

  • Diploma:  Philipps University Marburg (Chemistry)
  • Ph.D.:  Philipps University Marburg (Immunology)
  • Postdoctoral Fellow:  German Cancer Research Centre Heidelberg
  • Postdoctoral Fellow: Walter and ELIZA Hall Institute (Melbourne, Australia)
  • Groupleader:  German Cancer Research Centre Heidelberg
  • 1986: Habilitation, University of Heidelberg
  • since 1990: Professor of Immunobiology, Rhein.-Friedrich Wilhelms University of Bonn
  • 1992 to 2002: Speaker of the Graduiertenkolleg ”Functional protein domains”
  • 1995/96 Sabbatical at the Imperial Cancer Research Fund, London U.K.
  • 2002 Sabbatical at Monash University, Melbourne, Australia
  • 2005/06 Sabbatical at Otago University, NZ

 

Research Interest

  • Function and structure of MHC class II molecules
  • Molecular mechanism of the antigen processing pathway
  • The role of the chaperone invariant chain for MHC class II assembly
  • MHC class II polymorphism and peptide receptor formation
  • Herpes Simplex Type 1 immune evasion strategies
  • Regulation of components of the MHC class II processing pathway
  • Tumour vaccination

 

Technology and Methods

  • Immunochemistry, immunogenetics  and molecular biology
  • Gene transfer to eukaryotic cells
  • Flow cytometry (FACS)
  • cell culture of tumour and hybridoma cells

 

Research Summary

The focus of our interest is the investigation of MHC class II molecules. Their structure and function is explored by biochemical and molecular biology methods. We study the role of human HLA-encoded peptide receptors for initiation of immune responses.
HLA class II genes exhibit an unusually high polymorphism. At present, more than 1200 alleles of class II genes were identified. Recently, we discovered that class II subunits assemble to an oligomeric complex with the chaperone invariant chain (Ii), which consists of a class II heterodimer and an Ii trimer. Ii plays the role of an editor, which selects matched class II peptide receptor subunits from mismatched class II heterodimers. We developed a model describing a novel mechanism for assembly of class II molecules. This model is important to verify the composition of class II peptide receptors expressed on antigen presenting cells.

At present, we explore the composition and the genetic basis of a class II receptor family, which produced by a combination of subunits from different class II islotypes.
For this task, class II alleles are cloned and mutated to define members of the receptor family. Our aim is to unravel structural requirements that define the discovered receptor family.
 
The biosynthetic route of MHC class II molecules and the acquisition of antigenic peptides by class II molecules is designated as the antigen processing pathway. Some virus species target this processing pathway to prevent their elimination by the immune system. We study Herpes Simplex Type 1, which evades immune recognition by diversion of class II peptide receptors from their antigen processing route to a release by exosomes. The question was addressed, how HSV-1 operates in primary cells, such as dendritic cells to manipulate antigen presentation of viral antigens.

By introducing antigenic sequences into the peptide groove-binding sequence of invariant chain, we invented recombinant antigens for genetic vaccination. The mechanism of processing and presentation of these antigens still has to be unravelled.

We discovered that a gene located in the MHC class III region encodes a chaperone that impacts on the stability of components of the class II processing pathway. The regulatory network that we explore, partially explains co-regulation of MHCII genes by interferon gamma and the action of the transactivator CIITA.



Since more than 25 years our projects are continuously supported by the Deutsche Forschungsgemeinschaft. In addition we received financial support from the Volkswagen foundation, from the Deutsche Krebshilfe, from the Fonds of Chemical Industry and from the Sander foundation.

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