Molecular recognition mechanism of novel KIR2DS1 specific monoclonal antibodies [an abstract of entire text]

概要

Natural killer (NK) cells play critical roles in host defense against types of tumors, microbial infections, hematopoietic and solid organ transplantations and autoimmune diseases. The activation of NK-cell effector functions is regulated by multiple types of activating and inhibitory receptors, as designated as paired receptors, that recognize the ligands expressed on potential target cells. Killer cell immunoglobulin-like receptor (KIR) family consists of polymorphic but highly homologous receptors regulates human NK cell functions. Especially, two paired receptors against human leukocyte antigen (HLA)-C allotypes with Lys80, activating KIR2DS1 and inhibitory KIR2DL1, have only six different amino acid residues, and hard to be discriminated by monoclonal antibodies (mAbs). In our laboratory, three novel rat anti-KIR2DS1 specific mAbs were successfully generated. In this study, using surface plasmon resonance (SPR) and X-Ray crystallization, I studied the understanding of the molecular recognition mechanism of these original anti-KIR2DS1 mAbs for the basic research to clarify the expression properties of KIR2DS1 in the NK cell-related immune disorders, and future clinical applications in the effective regulation of NK cell functions.