BMC Seminar Thursday 15th December 2016, at 12:00 room 343 in Læknagarður

Speaker: Ásdís Kristinsdóttir Frost, Molecular Biologist, Landspítali University Hospital, Department of Genetics and Molecular Medicine

Title: Unraveling a novel mechanism of monoclonal antibodies targeting the serine protease inhibitor, HAI-1.

Abstract: Regulation of enzymatic activity in the human body by protein inhibitors is an important process in homeostasis. Serine proteases represent the largest group of proteases in the human body and are involved in numerous critical physiological functions, such as but not limited to; digestion, blood coagulation, apoptosis, signal transduction, reproduction and the immune response. Compromised regulation of serine protease activity may have grave consequences and is known to be involved in pathologies including skin diseases, tumorigenesis and metastasis.

A special kind of protease inhibitors is the Kunitz-type inhibitor hepatocyte growth factor activator inhibitor (HAI)-1, a membrane bound protease inhibitor that is co-expressed on cell surfaces with one of its target proteases, matriptase. Recent advances in structural information on the single domains of HAI-1 have opened up for detailed analysis on the function of these domains with the aim to understand the relationship between HAI-1 tertiary structure and function. We have developed monoclonal antibodies against the extracellular part of human recombinant HAI-1.

Presented here, is a study of a subset of monoclonal antibodies with affinity to the MANEC domain. We characterized the binding kinetics of the antibodies to HAI-1, mapped the epitope using SPR. Furthermore; we screened the antibodies for potential effects on HAI-1 function using biochemical assays. The high-affinity monoclonal antibodies appear to stimulate the anti-proteolytic activity of HAI-1, which is a novel mechanism of monoclonal antibodies. The antibodies thereby represent tools to potentially manipulate the tertiary structure of HAI-1. The antibodies also represent new powerful tools for the use in immuno-affinity chromatography and for immuno-detection techniques such as Western blotting.