Abstracts (complete list) - Wissenschaft Online

Björn Linke, Heiko Weyd, Lucie Dörner, Andrea Mahr, Peter H. Krammer
Structural Requirements for Annexin 1 Mediated Suppression
of Dendritic Cells
Peripheral tolerance comprises several mechanisms to prevent autoimmune disease. To
better understand molecular mechanisms of self-tolerance and nonresponsiveness
against apoptotic “self” cells we generated monoclonal antibodies against apoptotic
cells. We identified one monoclonal antibody which determined Annexin 1 as a new
signalling molecule on the surface of human apoptotic cells. Coculture experiments of
dendritic and apoptotic cells as well as incubation of dendritic cells with recombinant
Annexin 1 lead to inhibition of DC maturation.
The mechanism by which Annexin 1 mediates this effect remains to be studied further.
In an attempt to identify the active site of Annexin 1 we generated different deletion
constructs and mutants of Annexin 1. These proteins are analyzed for their capability to
modulate maturation of DCs. Their effect on cytokine secretion and expression of DC
surface markers including MHC and costimulatory molecules e.g. CD80 and CD86 and
their influence on T cell proliferation in DC-T cell cocultures are studied.
Furthermore, transwell experiments in our lab have shown that a direct cell contact
between apoptotic and dendritic cells is required for the inhibition of DC maturation. By
using photocrosslinking and immunoprecipitation we study the Annexin 1 receptor on
the surface of DCs.