B7-H5 costimulates human T cells via CD28H

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• The B7/CD28 family plays a critical role in modulating immune responses and is a key target for therapeutic drug development.
• Understanding novel costimulatory molecules is essential for advancing treatments for human diseases.

Purpose of the Study:

• To identify and characterize a novel CD28 homologue (CD28H) and its ligand involved in human immune regulation.
• To elucidate the functional consequences of the B7-H5/CD28H interaction on T-cell responses.

Main Methods:

• Screening of a receptor array to identify ligands for CD28H.
• Characterization of CD28H expression on T cells under different conditions.
• Analysis of the signaling cascade initiated by B7-H5/CD28H interaction.

Main Results:

• Identification of a novel CD28 homologue (CD28H) absent in mice but present on human naive T cells.
• Discovery of B7 homologue 5 (B7-H5) as the specific ligand for CD28H, expressed on macrophages and dendritic cells.
• Demonstration that B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via AKT signaling.

Conclusions:

• The B7-H5/CD28H axis represents a novel costimulatory pathway crucial for regulating human T-cell immunity.
• This pathway's unique role in human T-cell responses presents a promising target for developing immunotherapies.