CTLA-4 is a second receptor for the B cell activation antigen B7

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Optimal immune responses require T and B lymphocyte interactions.
• CD28, a T cell receptor, binds B7 on B cells, costimulating T cell activation.
• CTLA-4, a homolog of CD28, shares structural similarities but its function is unknown.

Purpose of the Study:

• To investigate the functional properties of CTLA-4.
• To determine if CTLA-4 shares functional properties with CD28, specifically binding to the B7 counter-receptor.
• To assess the impact of CTLA-4 binding on T and B lymphocyte interactions and immune responses.

Main Methods:

• Produced a soluble genetic fusion protein, CTLA4Ig, combining the extracellular domain of CTLA-4 with an immunoglobulin C gamma chain.
• Tested CTLA4Ig binding to B7-transfected cells and lymphoblastoid cells.
• Used immunoprecipitation to confirm CTLA4Ig interaction with B7.
• Measured the avidity of B7Ig fusion protein for CTLA4Ig.
• Assessed the inhibitory effect of CTLA4Ig on in vitro immune responses involving T and B lymphocytes.

Main Results:

• CTLA4Ig specifically bound to B7-transfected cells and lymphoblastoid cells.
• CTLA4Ig successfully immunoprecipitated B7 from cell surface extracts.
• The binding avidity between B7Ig and CTLA4Ig was determined to be approximately 12 nM (Kd).
• CTLA4Ig demonstrated potent inhibition of in vitro immune responses dependent on T and B lymphocyte interactions.

Conclusions:

• CTLA-4 binds to the B7 counter-receptor on activated B cells, a function shared with its homolog CD28.
• These findings provide direct evidence for CTLA-4's role in regulating T and B lymphocyte interactions.
• Lymphocyte interactions mediated by the B7 counter-receptor are crucial for in vitro alloantigen responses.