Molecular basis of epratuzumab antibody recognition of CD22 inhibitory clusters on B cells derived by integrative structural biology approaches.
Researchers at The Hospital for Sick Children (SickKids) have been exploring the molecular structure of immune cell components, and how gaining an understanding of their anatomical organization can help develop future targeted therapies for blood cancers and autoimmune diseases. Dr. Jean-Philippe Julien and co-authors, Dr. June Ereño-Orbea and Taylor Sicard provide the details of their study, “Molecular basis of human CD22 function and therapeutic targeting”, published October 2 in Nature Communications.
CD22 is a molecule found on the surface of B cells that helps regulate their survival. But to understand CD22, we first have to understand how the immune system works. The immune system uses several components to protect against infections from bacteria or viruses and one of these components are B cells. B cells help to control the immune system and when they don’t function properly, the immune system becomes unbalanced. This can result in devastating blood cancers such as lymphoma and leukemia, and autoimmune diseases such as rheumatoid arthritis and lupus. We’ve known for a while that CD22 is an important factor in autoimmune diseases and hyperactive B-cells. Yet, the 3D architecture of CD22 has remained elusive, preventing a molecular understanding of how it functions.
In this study, the scientists have characterized at high resolution the properties of the human CD22 molecule. The picture of its 3D architecture provides insights into the molecule’s role in preventing autoimmunity in mammals. The scientists have also gone one step further and provided blueprints of the specific site where a therapy targets CD22. Understanding the architecture and function of CD22 and other molecules uniquely present on the B cell provides an opportunity to improve health outcomes. The structural blueprints now provide the basis to better understand how treatments work and offer valuable clues for the design of new treatments for B-cell dysfunction.
The work was supported by grants from the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation (CFI) John R. Evans Leaders Fund, the Ontario Research Fund and SickKids Foundation. Dr. June Ereño-Orbea is a CIHR Banting and Restracomp Postdoctoral Fellow at SickKids. Taylor Sicard is a CIHR CGS-M recipient and Restracomp Ph.D. candidate in the Department of Biochemistry at the University of Toronto.