Marion H Brown

Molecular interactions of leukoctye surface receptors

We study how immune regulation depends on molecular interactions of leukocyte surface receptors. The overall effect of a receptor can vary from activation to inhibition. It is critical to understand how this is controlled to interpret the role of a receptor in a complex biological system and for designing therapeutic intervention in autoimmune diseases and cancer. By studying selected receptors, we aim to identify both the specific niche the receptors occupy and the general paradigms.

CD6 binding the receptor CD166 and the adaptor, SLP-76.

We have developed methods for detecting low affinity interactions at cell surfaces. This led to the identification of the CD200/CD200R, CD47/SIRPalpha and CD48/2B4 interactions. All these interactions are being studied as therapeutic targets. One leukocyte surface receptor may interact with more than one extracellular or intracellular ligand. Thus it is important to establish a hierarchy as to which interaction occurs in a given setting. We have quantified interactions using surface plasmon resonance, which then allows us to relate the role of the interaction to functional outcomes in cellular experiments.

We currently focus on two families of leukocyte surface receptors: the CD2/SLAM family, and two receptors with scavenger receptor cysteine rich domains, CD5 and CD6. These receptors mediate interacts between cells through homophilic or heterophilic interactions. CD6 binds the cell surface receptor CD166 and the SH2 domain-containing adaptor SLP-76.

Relevant Publications

Chappell PE, Garner LI, Yan J, Metcalfe C, Hatherley D, Johnson S, Robinson CV, Lea SM, Brown MH.

Structure. 23: 1426–1436.

Margraf S, Garner LI, Wilson TJ, Brown MH.

Immunology. doi: 10.1111/imm.12513 (Epub ahead of print)

Wilson, T.J., L.I. Garner, C. Metcalfe, E. King, S. Margraf, and M.H. Brown

PLoS One 9: e92184.

Mihrshahi, R. and M.H. Brown

J Immunol. 185: 7216-22.

Research Areas