B7-H5 costimulates human T cells via CD28H

Nat Commun. 2013;4:2043. doi: 10.1038/ncomms3043.

Abstract

The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD28 Antigens / chemistry
  • CD28 Antigens / metabolism*
  • Coculture Techniques
  • Epitopes / immunology
  • Fluoresceins / metabolism
  • Gene Expression Regulation / drug effects
  • Genome, Human / genetics
  • HEK293 Cells
  • Humans
  • Ligands
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Phosphotyrosine / metabolism
  • Protein Binding / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Succinimides / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Vanadates / pharmacology

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • CD28 Antigens
  • Epitopes
  • Fluoresceins
  • GI24 protein, human
  • Ligands
  • Membrane Proteins
  • Succinimides
  • TMIGD2 protein, human
  • pervanadate
  • Phosphotyrosine
  • Vanadates