THE LEUKOCYTE NEURON CELL-SURFACE ANTIGEN OX2 BINDS TO A LIGAND ON MACROPHAGES/

The OX2 membrane glycoprotein contains two immunoglobulin superfamily (IgSF) domains and seems likely to interact with other cell surface pr oteins. A soluble chimeric protein with the two IgSF domains of OX2 en gineered onto domains 3 + 4 of rat CD4 antigen was expressed. To detec t possible weak interactions, the chimeric protein was coupled to fluo rescent covaspheres(TM) to provide a highly avid display of OX2. The O X2 covaspheres bound macrophages but not other cell types. The specifi city of the interaction was demonstrated by blocking with Fab fragment s of the OX2 monoclonal antibody (mAb). A new mAb, MRC OX88, was raise d against macrophages which also blocked the interaction and presumabl y recognizes the ligand. The epitope for the MRC OX2 mAb and a site fo r Ligand binding were mapped to domain 1 by site-directed mutagenesis. The OX2 antigen is present on thymocytes, some lymphocytes, neurons a nd endothelial cells; thus, it has the potential to mediate interactio ns between these ce:ll types and macrophages.