The Immunoglobulin Superfamily Receptome Defines Cancer-Relevant Networks Associated with Clinical Outcome

Abstract

Highlights d The immunoglobulin superfamily (IgSF) interactome identifies over 500 receptor pairs d The IgSF interactome reveals receptor-ligand communities dysregulated in cancer d More than 60 receptor-ligand pairs confirmed using orthogonal methods d Interacting protein signatures are correlated with clinical outcome

Unbiased Identification of Extracellular Protein–Protein Interactions for Drug Target and Biologic Drug Discovery

“…However, using enzymatic readouts can add a high degree of signal amplification that allows for increased sensitivity. Therefore, the approach used to generate the largest ePPI networks to date uses pentamerization combined with an enzymatic β-lactamase colorimetric assay [37][38][39][40]. As for bead-based approaches, the specific readout can be magnetic, fluorescent or chemiluminescent depending on the specific screening method used [41,42].…”

“…Using conditioned media involves direct capture of secreted protein or protein ectodomains in the absence of protein purification, thus minimizing potential inactivation of the proteins due to purification steps. The use of conditioned media can also save time and resources, helping to make the approaches more accessible to different laboratory and more amenable to scaling up [37][38][39][40].…”

“…While purified proteins can be used, plate-based formats allow for the direct capture of secreted tagged proteins from conditioned media. Capture of biotinylated proteins using streptavidin-coated plates [37] or Fc-tagged proteins using Protein A-coated plates [38][39][40] followed by washing allows for the effective purification of library proteins Unbiased Identification of Extracellular Protein-Protein Interactions for Drug Target… DOI: http://dx.doi.org/10.5772/intechopen.97310 in wells while adding sensitivity by multimerizing (in the case of multivalent binding of streptavidin to biotin) or capturing already multimerized proteins. This approach also allows the use of enzymatic liquid phase readouts: β-lactamase-based colorimetric assays or luciferase-based luminescence assays which provides an additional degree of signal amplification.…”

Applications and analytical tools of cell communication based on ligand-receptor interactions at single cell level

“…However, continuous update of current ligand-receptor libraries is necessary to cover more information of receptors, ligands and their interactions. Recently, receptor study of immunoglobulin superfamily (IGSFF) identified more than 60 new pairs of ligand -receptor [ 84 ]. The ligand-receptor pairs network is not completely understood and still needs futher exploration and improvement.…”

Immune recognition of phosphoantigen‐butyrophilin molecular complexes by γδ T cells

“…A recent study undertook a large-scale ligand discovery campaign for Ig superfamily proteins and identified a new candidate binding partner for BTN2A1, FAM187B, plus eight new potential binding partners for BTN3A, so it will be very interesting to see if any of these molecules have a role in pAg or γδ T cell biology. 76 These are the next fundamental questions that must be answered in order to develop a better understanding of the pAg-sensing system, which is turning out to be highly distinct from all other characterized modes of Ag recognition.…”