Determination of the inhibitory activity and biological half-live of soluble CD83: comparison of wild type and mutant isoforms.
A soluble form of CD83 ("sCD83") has been shown to block DC-mediated T cell stimulation in vitro and an immunosuppressive role has also been shown in vivo using an experimental-autoimmune-encephalomyelits (EAE) model. Using recombinant mutational analyses, recently, we could show that sCD83 forms a homo-dimer, whereby four cysteines are involved in the intra-molecular disulfide bonds and the fifth cysteine is responsible for the inter-molecular bridging of the two molecules. Further studies revealed that the two CD83-isoforms, i.e. the dimer and the monomer, have a similar inhibitory capacity when tested in vitro. Here we show that the biological (in vivo) half-life of the two sCD83 isoforms is comparable and was between 2 and 3h. In addition, using the EAE-model, we were able to show that a monomeric-mutant isoform of soluble CD83 has a similar inhibitory activity in vivo when compared with a dimeric-wildtype isoform.
Zinser
Elisabeth
E
Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany. Elisabeth.Zinser@derma.imed.uni-erlangen.de
Lechmann
Matthias
M
Golka
Antje
A
Hock
Barry
B
Steinkasserer
Alexander
A
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019281:Dimerization; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D000097802:CD83 Antigen