MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1.
Tissue-specific homing of lymphocytes is regulated by interactions with the endothelium of specialized venules, such as the high endothelial venules (HEV) in lymph nodes and mucosal lymphoid tissues. The mucosal vascular addressin, a 58-66K glycoprotein adhesion receptor for lymphocytes, is selectively expressed on HEV of mucosal lymphoid organ and on lamina propria venules and helps direct lymphocyte traffic to these mucosal tissues. We now report the isolation of a complementary DNA that, on transfection into COS cells, encodes immunoreactive addressin 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-terminal domains that display strong homology to previously described vascular adhesion receptors for leukocytes, ICAM-1 (ref. 6) and VCAM-1 (ref. 7). The membrane proximal domain is homologous to the third domain (C alpha 2) of another mucosa-associated immunoglobulin family member, IgA1 (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 multidomain receptor displaying several structural motifs that may participate in lymphocyte homing interactions.
Department of Pathology, Stanford University, California 94305.
M J
MJ
Briskin
L M
LM
McEvoy
E C
EC
Butcher
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000235:genetics; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D004247:DNA; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000737:chemistry*; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D009088:Mucoproteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009077:Mucins; D009088:Mucoproteins; D004247:DNA