Cell surface receptors are glycoproteins that are embedded or otherwise attached to the cell’s plasma membrane and have a binding site for specific ligands (cytokines, hormones, growth factors, neurotransmitters, adhesion molecules, etc.) exposed to the extracellular environment. Ligand binding to a cell surface receptor generally leads to a biological signal that is propagated from the receptor toward the cell interior, resulting in a cellular response such as proliferation, differentiation, apoptosis, degranulation, etc. Cell surface receptors transduce ligand signals by a variety of mechanisms such as receptor clustering, activation of a hidden enzymatic activity, opening of ion channels, etc.
Cell surface receptors pose specific challenges to antibody development as most are not available in quantities sufficient for immunization unless generated artificially by recombinant gene expression. Many receptors such as G-protein coupled receptors (GPCR) traverse the membrane several times and cannot be expressed as recombinant soluble fragments. The binding geometry between receptor and antibody is critical in determining the biological effect of the antibody (i.e., whether it may be blocking, neutralizing, activating or not interfering with receptor function). Glycosylation of a cell surface receptor can further compound antibody design.
Membrane proteins are ~ 25% of the genome
High Throughput Cell Surface Antigen Screening
Antibody Solutions pioneered development of a high-throughput primary screening platform for the isolation of monoclonal antibodies to cell surface antigens.
Identification of a clone producing an antibody that binds to a cell surface antigen (upper panel) vs. a control (lower panel) by flow cytometry.