The Study Of Selective Binding BAFF/APRIL By BCMA

Clinical studies showed that the dysregulation of BAFF/APRIL is involved in the pathogenesis of B-cell related diseases.Nowadays,blockade of BAFF/APRIL binding to their receptors by antagonists have become the therapeutic strategies in the treatment of autoimmune disorders.At the same time,these drugs also with some problems such as: unsatisfied effect,increased susceptibility to infection.So,it is still need further research about BAFF/APRIL system.BAFF and APRIL share two common receptors: BCMA and TACI.It was reported that BCMA shows higher affinity for APRIL than for BAFF.The ligand binding specificity of receptors appears to be determined by interactions outside Dx L common motif.Based on previous research,in this study,the cysteine-rich domains(CRDs)of BCMA and TACI was divided into two segments: BCMA1,BCMA2,TACI1 and TACI2,and these four peptides were synthetized.BCMA1 and TACI1 contain the conservative Dx L domain while BCMA2 and TACI2 are the segments outside the main functional area.The BCMA1 was fused with human IgG1 Fc segment as BCMA1-Fc fusion protein.The role of BCMA2 in the slevtivity ligand bingding of BCMA was explored by ELISA test.The results show that the peptide BCMA2 could only inhibite BCMA-Fc binding with mAPRIL,could not inhibit the interaction of BCMA-Fc with BAFF and TACI-Fc with the two ligands.By contrast,the inhibition rates of the peptide TACI2 on the reaction of BCMA-Fc with two ligands and TACI-Fc with two ligands are keeping at 22%-26%.The affinity of BCMA1-Fc binding with mAPRIL was significantly affected by the knockout of BCMA2.The peptide BCMA2 has no inhibiting effect on the interaction of BCMA1-Fc with BAFF,but it appeared slightly inhibiting effect on the interaction of BCMA1-Fc with mAPRIL at high concentrations.Based on the above results,we concluded that BCMA2 makes significant contribution to BCMA selective binding APRIL,and the binding site of BCMA2 are located outside the conservative hydrophobic pocket of APRIL.