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Published on: April 23, 2017
A ligand for human CD48 on epithelial cells
C J Ianelli1, C M Edson, D A Thorley-Lawson
1Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Insights
Researchers identified a novel ligand for human CD48 on epithelial cells, challenging previous understanding. This discovery suggests CD48 may mediate lymphocyte-epithelial cell interactions.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD48, an immunoglobulin superfamily member, shares homology with CD58.
- In rodents, CD48 binds CD2, but human CD48 ligand remained elusive.
- Previous research indicated CD58 as the human CD2 ligand.
Purpose of the Study:
- To identify the ligand for human CD48.
- To investigate the role of CD48 in cell adhesion.
- To explore the interaction between CD48 and epithelial cells.
Main Methods:
- Utilized a decameric, soluble CD48 IgM fusion protein to detect epithelial cell binding.
- Employed monomeric CD48 immobilized on plastic dishes for binding assays.
- Generated monoclonal antibodies (mAbs) against the identified ligand to block CD48 binding.
- Investigated the role of CD44 in CD48-epithelial cell interactions.
Main Results:
- Demonstrated the presence of a CD48 ligand on epithelial cells.
- Confirmed that epithelial cells bind to both soluble and immobilized CD48.
- Monoclonal antibodies against the ligand effectively blocked CD48 binding to epithelial cells.
- Showed that CD44, specifically its glycosaminoglycan binding site, plays an auxiliary role in CD48 binding.
- Found no interaction between human CD48 and CD2.
Conclusions:
- Human CD48 functions as an adhesion molecule by binding to a ligand on epithelial cells.
- CD44 assists in the binding of epithelial cells to CD48.
- This interaction suggests a novel role for CD48 in lymphocyte-epithelial cell communication.
Abstract:
CD48 is a member of the Ig superfamily with a high degree of sequence homology to CD58 (LFA-3). In rodents, CD48 is the ligand for CD2 whereas in humans, CD58 is the ligand for CD2. Despite intensive efforts, no ligand for human CD48 has been convincingly demonstrated. We now show that a ligand for human CD48 is present on epithelial cells. The ligand was detected based on the ability of epithelial cells to bind both a decameric, soluble CD48 IgM fusion protein and monomeric CD48 immobilized on plastic dishes. mAbs raised to the ligand completely block binding of CD48 to all epithelial cells tested. We further show that the cell surface proteoglycan CD44 plays an auxiliary role in the binding of epithelial cells to CD48 and that this interaction involves the glycosaminoglycan binding site of CD44. No interaction of human CD48 with CD2 was detected. This is the first clear demonstration that human CD48 can function as an adhesion molecule and suggests a role for CD48 in lymphocyte epithelial cell interactions.
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