Abstract
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.
MeSH terms
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Activated-Leukocyte Cell Adhesion Molecule
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Antibodies, Monoclonal / pharmacology
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Antibody Specificity
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism*
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Binding Sites
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Cell Adhesion Molecules / metabolism*
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Epitopes
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Glycoproteins / metabolism*
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Humans
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Membrane Proteins*
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Binding / drug effects
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Receptors, Lipoprotein*
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Receptors, Scavenger
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Recombinant Fusion Proteins / metabolism
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Scavenger Receptors, Class B
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Structure-Activity Relationship
Substances
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Activated-Leukocyte Cell Adhesion Molecule
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD6 antigen
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Cell Adhesion Molecules
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Epitopes
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Glycoproteins
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Membrane Proteins
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Peptide Fragments
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Receptors, Immunologic
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Receptors, Lipoprotein
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Receptors, Scavenger
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Recombinant Fusion Proteins
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Scarb1 protein, mouse
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Scavenger Receptors, Class B