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 3 h. 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.