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Updated: Aug 11, 2026
Murine Model of CD40-activation of B cells
Published on: March 6, 2010
Expression and function of the costimulatory molecule B7 on murine Langerhans cells: evidence for an alternative
Z Razi-Wolf1, L D Falo, H Reiser
1Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
Insights
Murine Langerhans cells (LC) express a non-murine B7 (mB7) ligand for CTLA-4, which is functional and contributes to T cell activation. This suggests LC may possess additional costimulatory ligands beyond the mB7 family, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Murine B7 (mB7) is a key costimulatory molecule for CD4+ T cell activation.
- CTLA-4 receptors bind to mB7 and another spleen cell ligand.
- Langerhans cells (LC) are critical antigen-presenting cells in the skin.
Purpose of the Study:
- To investigate the expression and function of CTLA-4 ligands on murine Langerhans cells (LC).
- To determine if non-mB7 CTLA-4 ligands on LC are functional and contribute to T cell responses.
- To explore the potential for additional costimulatory ligands on LC.
Main Methods:
- Utilized anti-mB7 monoclonal antibody (mAb) 16-10A1 and human CTLA4Ig (hCTLA4Ig) to detect antigens on cultured LC.
- Assessed the binding of hCTLA4Ig to LC after preincubation with anti-mB7 mAb.
- Performed functional studies using alloreactive and antigen-specific T cell responses to evaluate the inhibitory effects of mAbs and hCTLA4Ig.
Main Results:
- Cultured LC, but not freshly isolated LC, expressed antigens recognized by anti-mB7 mAb and hCTLA4Ig.
- Anti-mB7 mAb did not block hCTLA4Ig binding, indicating the presence of at least one other CTLA-4 ligand on cultured LC.
- hCTLA4Ig demonstrated superior inhibition of LC costimulatory activity compared to anti-mB7 mAb for both alloreactive and antigen-specific T cells.
- Combined inhibition with anti-mB7 mAb and hCTLA4Ig did not completely abolish LC activity, suggesting the existence of other costimulatory ligands.
Conclusions:
- Cultured murine Langerhans cells express a functional, non-mB7 ligand for CTLA-4 that contributes to T cell activation.
- This non-mB7 ligand plays a role in the immune response induction by LC.
- Langerhans cells may express additional, yet unidentified, costimulatory ligands beyond the mB7 family, warranting further investigation.
Abstract:
We have previously shown, through transfection experiments, that the murine B7 (mB7) molecule, a ligand for the CD28 and CTLA-4 receptors, is a sufficient costimulatory signal for the antigen-specific and major histocompatibility complex (MHC)-restricted activation of murine CD4+ T lymphocytes. In addition to mB7, another ligand with affinity for CTLA-4 has been described on spleen cells. Here we report our studies on the expression and function of these molecules on murine Langerhans cells (LC). Both anti-mB7 monoclonal antibody (mAb) 16-10A1 and human CTLA4Ig (hCTLA4Ig), a chimeric fusion protein consisting of the extracellular domain of human CLTA-4 and the constant domain of human IgG1, detected antigen(s) on cultured but not freshly isolated LC. Preincubation of cultured LC with anti-mB7 mAb did not significantly affect binding of hCTLA4Ig to these cells. This result demonstrate the existence of at least one other ligand for the CLTA-4 receptor on cultured LC. Functional studies revealed that the costimulatory activity of LC was inhibited better by hCTLA4Ig than by the anti-mB7 mAb. This differential effect was seen in the case of both alloreactive and antigen-specific, syngeneic T cell responses. These findings suggest that the non-mB7-ligand for CTLA-4 is functional and participates in the induction of immune responses by LC. Importantly, even synergistic combinations of anti-mB7 mAb and hCTLA4Ig did not inhibit completely the activity of LC. These findings therefore raise the possibility that LC express other costimulatory ligands besides mB7 and related family members.
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