Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.
Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 monoclonal antibody (mAb) or with a mAb (J4-81) that recognized a TE cell antigen. We isolated and expressed a cDNA clone encoding this antigen and show that COS cells transfected with this cDNA bind a CD6 immunoglobulin fusion protein (CD6-Rg). This antigen, which we named ALCAM (activated leukocyte-cell adhesion molecule) because of its expression on activated leukocytes, appears to be the human homologue of the chicken neural adhesion molecule BEN/SC-1/DM-GRASP. The gene was mapped to human chromosome 3q13.1-q13.2 by fluorescence in situ hybridization of cDNA probes to metaphase chromosomes. We prepared an ALCAM-Rg fusion protein and showed that it binds to COS cell transfectants expressing CD6, demonstrating that ALCAM is a CD6 ligand. The observations that ALCAM is also expressed by activated leukocytes and that both ALCAM and CD6 are expressed in the brain suggest that ALCAM-CD6 interactions may play a role in the binding of T and B cells to activated leukocytes, as well as in interactions between cells of the nervous system.
Bowen
M A
MA
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Patel
D D
DD
Li
X
X
Modrell
B
B
Malacko
A R
AR
Wang
W C
WC
Marquardt
H
H
Neubauer
M
M
Pesando
J M
JM
Francke
U
U
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D002522:Chlorocebus aethiops; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D016384:Consensus Sequence; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008024:Ligands; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D020410:Activated-Leukocyte Cell Adhesion Molecule; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008024:Ligands; D011993:Recombinant Fusion Proteins