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B70 antigen is a second ligand for CTLA-4 and CD28
1Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Nature
|November 4, 1993
Summary
Researchers identified B70, a novel protein that acts as a second ligand for CD28 and CTLA-4. This discovery is crucial for understanding T-cell costimulation in immune responses.
Area of Science:
- Immunology
- Molecular Biology
Background:
- The B7/BB1 antigen interacts with CD28 on T cells, providing costimulation for T-cell activation.
- Previous research suggested a second ligand for CD28 and CTLA-4 due to antibody discrepancies.
Purpose of the Study:
- To identify and characterize a potential second ligand for CD28 and CTLA-4.
- To investigate the role of this new ligand in T-cell costimulation.
Main Methods:
- Generated a monoclonal antibody (IT2) targeting a 70K glycoprotein (B70).
- Cloned B70 complementary DNA and analyzed its protein structure.
- Assessed B70 expression on various immune cells.
- Investigated the inhibitory effects of IT2 on CTLA-4 binding and mixed lymphocyte responses.
Main Results:
- Identified B70, a novel immunoglobulin superfamily protein, with limited homology to B7.
- B70 is expressed on monocytes, dendritic cells, and activated T, NK, and B lymphocytes.
- The IT2 antibody blocked CTLA-4 binding and inhibited primary allogeneic mixed lymphocyte responses, especially when combined with anti-B7 antibody.
Conclusions:
- B70 functions as a second ligand for CD28 and CTLA-4.
- B70 plays a significant role in T-cell costimulation during primary immune responses.