Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule

Lymphocyte migration to lymphoid organs involves organ-specific homing receptors. The mouse peripheral lymph node homing receptor, defined by the MEL-14 monoclonal antibody (mAb), is a lectin-like cell surface protein, which is rapidly down-regulated upon cell activation with phorbol 12-myristate 13-acetate. We have raised mAbs against rapidly shed molecules released from the cell surface of activated human leukocytes. Five mAbs, DREG-55, -56, -110, -152, and -200, define an 80- to 85-kDa molecule involved in human lymphocyte recognition of peripheral lymph node (PLN) high endothelial venules (HEVs). The DREG-56 mAb specifically inhibits greater than 90% of binding of human lymphocytes to HEVs within frozen sections of peripheral but not mucosal lymphoid tissue. Furthermore, the gp80 antigen is expressed on lymphoid cell lines that are capable of binding to PLN HEVs. The DREG-56 mAb also inhibits lymphocyte binding of the phosphomannan monoester core from Hansenula hostii Y-2448, an activity associated with human and mouse lymphocyte recognition of PLN HEVs. Finally, all five DREG mAbs specifically stain COS cells transfected with LAM-1 cDNA, a putative human homologue of mouse MEL-14 antigen. These results demonstrate that the DREG mAbs define a human lymphocyte homing receptor for PLN HEVs and indicate that this human antigen is homologous to the MEL-14-defined murine lymphocyte homing receptor.