Increased survival and reduced renal injury in MRL/lpr mice treated with a human Fcγ receptor II (CD32) peptide.

Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease affecting many organs. The deposition in kidney tissue of immune complexes and their interaction with macrophages is thought to trigger the inflammatory response leading to glomerulonephritis. It has been demonstrated that inhibition of this interaction in murine models can alleviate the disease. Six synthetic peptides were derived from the membrane-proximal extracellular domain (EC2) of human Fcγ receptor II (huFcγRII). Of these, one peptide, huRII6, was shown to be a potent competitive inhibitor of IgG binding to recombinant FcγRII in vitro. To examine the possible therapeutic impact of huRII6 in vivo, this peptide, or a control, was given by subcutaneous injection to female MRL/lpr mice from weeks 7 to 36, resulting in an enhanced survival rate compared with control-treated animals and a reduction of proteinuria. Histopathological examination of the kidneys showed a reduction in deposition of immune complexes and preservation of structure. Such a functional peptide should prove useful for examining the role of IgG-FcγR interactions in experimental models of disease and may provide for the development of FcR-targeting drugs to treat autoimmune disorders.

Identification of a linear epitope for Fc-binding in the mouse FcγRIII.

Fc receptors are transmembrane proteins, found on the surfaces of immune cells, that aid in the removal of foreign pathogens by binding to antibody-coated targets via the Fc regions of the antibodies. To identify sites on mouse FcgammaRIII (moFcgammaRIII) alpha-chain that bind to the Fc region, peptides derived from the proximal extracellular domain (EC2) of moFcgammaRIII alpha-chain corresponding to the homologous region of human FcgammaRIIIB alpha-chain were synthesized. Binding of mouse IgG to the different peptides was tested by Dot-blot assay. The effective peptide (119)SFFHNEKSVRYH(130) located in the putative C-C' loop of the EC2 domain was found to bind mouse IgG specifically with an affinity of approximately 5.58 x 10(-5) M and inhibit the binding of mouse IgG to the receptor. Such a functional peptide should be very useful for further understanding the IgG-FcgammaR interaction and development of FcR-targeting drugs.