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Identification of a costimulatory molecule rapidly induced by CD40L as CD44H
1Michael Heidelberger Division of Immunology, Department of Pathology, New York University Medical Center, New York 10016, USA.
Insights
CD40 ligand interaction with CD40 activates T and B cells. Researchers found CD44H is a novel costimulatory molecule, rapidly induced by CD40L, promoting T cell proliferation independently of CD28.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The CD40 ligand (CD40L) and CD40 interaction is crucial for T and B cell activation.
- This interaction induces a costimulatory activity distinct from the B7/CD28 pathway.
Purpose of the Study:
- To investigate the molecular basis of CD40L-induced costimulatory activity.
- To identify the novel costimulatory molecule involved in T cell activation.
Main Methods:
- Production of a monoclonal antibody (TM-1) targeting the costimulatory molecule.
- Expression cloning to identify the molecule bound by TM-1.
- Functional assays using Chinese hamster ovary (CHO) cells expressing CD44H.
Main Results:
- TM-1 binds an 85-kilodalton costimulatory molecule, identified as CD44H.
- CD44H expressed on CHO cells demonstrated potent costimulatory activity for T cell clonal expansion.
- This costimulation was observed in T cells from both wild-type and CD28-deficient mice, confirming a CD28-independent mechanism.
Conclusions:
- CD44H is a novel costimulatory molecule rapidly induced by CD40L.
- CD44H plays a significant role in T cell proliferation through a CD28-independent pathway.
- These findings reveal a new mechanism of immune cell activation mediated by CD44H.
Abstract:
The interaction between CD40 ligand and CD40 is critical for activation of T and B cells in vivo. We have recently demonstrated that this interaction rapidly induces a novel costimulatory activity distinct from B7 and independent of CD28. To study the molecular basis of the costimulatory activity, we have produced a novel monoclonal antibody, TM-1, that binds an 85-kilodalton costimulatory molecule rapidly induced by CD40L. Expression cloning reveals that TM-1 binds CD44H. CD44H expressed on Chinese hamster ovary cells has potent costimulatory activity for clonal expansion of T cells isolated from both wild-type mice and these with a targeted mutation of CD28. Thus, CD44H costimulates T cell proliferation by a CD28-independent mechanism. These results revealed that CD44H is a costimulatory molecule rapidly induced by CD40L.