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Programmed Cell Death-1 (PD-1) anchoring to the GPI-linked co-receptor CD48 reveals a novel mechanism to modulate

Della White1, Alexandra Cote-Martin1, Marina Bleck1

  • 1Departments of Immunology and Respiratory Research, USA.

Molecular Immunology
|March 8, 2023
PubMed

Insights

CD48, a coreceptor, activates PD-1 signaling, inhibiting T cell proliferation and cytokine production. This discovery offers a new strategy for developing therapies targeting immune-mediated diseases by modulating inhibitory checkpoint receptors.

Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Programmed cell death protein 1 (PD-1) activation is a therapeutic strategy for autoimmune diseases.
  • T cell activation is regulated by co-receptors and signaling pathways.

Purpose of the Study:

  • To investigate the role of CD48 in PD-1 activation and its functional consequences on T cells.
  • To explore CD48-dependent PD-1 activation as a novel therapeutic mechanism.

Main Methods:

  • Utilizing bead-conjugated antibodies to induce crosslinking and activate PD-1.
  • Employing primary human T cells and Jurkat T cells for functional assays.
  • Measuring T cell proliferation, IL-2 and IL-10 secretion, and NFAT activation.

Main Results:

  • CD48, but not CD71, induced Src kinase-dependent activation of PD-1 upon crosslinking.
  • CD48-dependent PD-1 activation inhibited proliferation of antigen receptor-induced T cells.
  • PD-1 activation via PD-1/CD48 bispecific antibodies reduced IL-2 and NFAT, and enhanced IL-10 secretion.

Conclusions:

  • CD48-dependent PD-1 activation provides a novel mechanism for fine-tuning T cell responses.
  • Anchoring PD-1 to co-receptors like CD48 offers a framework for developing new immunotherapies for immune-mediated diseases.
Keywords:
Immuno-receptor agonismNovel immuno-modulationProgrammed Cell Death-1 (PD-1)T cell inhibition

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