B7-H2 Is a Costimulatory Ligand for CD28 in Human

Sheng Yao, Yuwen Zhu, Gefeng Zhu, Mathew Augustine, Linghua Zheng, Diana J. Goode, Megan Broadwater, William Ruff, Sarah Flies, Haiying Xu, Dallas Flies, Liqun Luo, Shengdian Wang, Lieping Chen

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


CD28 and CTLA-4 are cell surface cosignaling molecules essential for the control of T cell activation upon the engagement of their ligands B7-1 and B7-2 from antigen-presenting cells. By employing a receptor array assay, we have demonstrated that B7-H2, best known as the ligand of inducible costimulator, was a ligand for CD28 and CTLA-4 in human, whereas these interactions were not conserved in mouse. B7-H2 and B7-1 or B7-2 interacted with CD28 through distinctive domains. B7-H2-CD28 interaction was essential for the costimulation of human T cells' primary responses to allogeneic antigens and memory recall responses. Similar to B7-1 and B7-2, B7-H2 costimulation via CD28 induced survival factor Bcl-xL, downregulated cell cycle inhibitor p27kip1, and triggered signaling cascade of ERK and AKT kinase-dependent pathways. Our findings warrant re-evaluation of CD28 and CTLA-4's functions previously attributed exclusively to B7-1 and B7-2 and have important implications in therapeutic interventions against human diseases.

Original languageEnglish (US)
Pages (from-to)729-740
Number of pages12
Issue number5
StatePublished - May 27 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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