MADCAM-1 HAS HOMOLOGY TO IMMUNOGLOBULIN AND MUCIN-LIKE ADHESION RECEPTORS AND TO IGA1

TISSUE-SPECIFIC homing of lymphocytes is regulated by interactions wit h the endothelium of specialized venules, such as the high endothelial venules (HEV) in lymph nodes and mucosal lymphoid tissues1-3. The muc osal vascular addressin, a 58-66K glycoprotein adhesion receptor for l ymphocytes, is selectively expressed on HEV of mucosal lymphoid organ and on lamina propria venules and helps direct lymphocyte traffic to t hese mucosal tissues4,5. We now report the isolation of a complementar y DNA that, on transfection into COS cells, encodes immunoreactive add ressin that specifically binds the mucosal HEV-binding T-cell lymphoma TK1. The predicted amino-acid sequence defines the mucosal addressin as a novel immunoglobulin family member, MAdCAM-1, with two amino-term inal domains that display strong homology to previously described vasc ular adhesion receptors for leukocytes, ICAM-1 (ref. 6) and VCAM-1 (re f. 7). The membrane proximal domain is homologous to the third domain (Calpha2) of another mucosa-associated immunoglobulin family member, I gA1 (refs 8, 9). In addition to the immunoglobulin domains, there is a serine/threonine-rich region which may serve as a backbone to present carbohydrate ligands to lymphocytes. MAdCAM-1 is thus a complex multi domain receptor displaying several structural motifs that may particip ate in lymphocyte homing interactions.