Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function

The OX2 membrane glycoprotein (CD200) is expressed on a broad range of tiss ues including lymphoid cells, neurons, and endothelium. We report the chara cterization of an OX2 receptor (OX2R) that is a novel protein restricted to cells of the myeloid lineage. OX2 and its receptor are both cell surface g lycoproteins containing two immunoglobulin-like domains and interact with a dissociation constant of 2.5 mu M and k(off) 0.8 s(-1), typical of many le ukocyte protein membrane interactions. Pervanandate treatment of macrophage s showed that OX2R could be phosphorylated on tyrosine residues. Blockade o f the OX2-OX2R interaction with an OX2R mAb exacerbated the disease model e xperimental allergic encephalomyelitis. These data, together with data from an OX2-deficient mouse (R.M. Hoek et al., submitted), suggest that myeloid function can be controlled in a tissue-specific manner by the OX2-OX2R int eraction.