The membrane-proximal scavenger receptor cysteine-rich domain of CD6 contains the activated leukocyte cell adhesion molecule binding site.
Binding studies with a CD6 immunoglobulin fusion protein (CD6 Rg) resulted in the identification and cloning of a CD6 ligand. This ligand was found to be a member of the immunoglobulin supergene family and was named ALCAM (activated leukocyte cell adhesion molecule). Cell adhesion assays showed that CD6-ALCAM interactions mediate thymocyte-thymic epithelium cell binding. ALCAM is also expressed by activated leukocytes and neurons and may be involved in interactions between T cells and activated leukocytes and between cells of the immune and nervous systems, respectively. Herein we describe the preparation of domain-specific murine CD6 Rg fusion proteins and show that the membrane-proximal SRCR (scavenger receptor cysteine-rich) domain of CD6 contains the ALCAM binding site. We also show that mAbs which bind to this domain preferentially block CD6-ALCAM binding. These results demonstrate that the membrane-proximal SRCR domain of CD6 is necessary for CD6 binding to ALCAM and provide the first direct evidence for the interaction of an SRCR domain with a ligand.
Whitney
G S
GS
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Starling
G C
GC
Bowen
M A
MA
Modrell
B
B
Siadak
A W
AW
Aruffo
A
A
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D000939:Epitopes; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051122:Scavenger Receptors, Class B; D013329:Structure-Activity Relationship
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D015815:Cell Adhesion Molecules; D000939:Epitopes; D006023:Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D011993:Recombinant Fusion Proteins; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B