Lymphocyte cell-cycle inhibition by HLA-G is mediated by phosphatase SHP-2 and acts on the mTOR pathway

Farah Ketroussi, Massimo Giuliani, Rajia Bahri, Bruno Azzarone, Bernard Charpentier, Antoine Durrbach

Research output: Contribution to journalArticlepeer-review

Abstract

Human leukocyte antigen G (HLA-G) is involved in regulating T-cell responses through its interaction with inhibitory receptors belonging to the immunoglobulin-like transcript family (ILT). In this context, we investigated the pathways involved in the control of cell-cycle entry of T cells following HLA-G interaction with its inhibitory receptor. We show that HLA-G acts through its interaction with the LILRB1 receptor expressed on T lymphocytes. Both HLA-G and LILRB1 antibodies block the inhibitory effect of HLA-G and restore T-cell proliferation. The interaction of HLA-G with T lymphocytes is associated with phosphorylation of SHP-2 phosphatase, but not SHP-1. In addition, in activated T cells, their incubation with HLA-G is not associated with a decrease in the TCR or CD28 downstream pathways, but is associated with dephosphorylation of the mTOR molecule and p70S6K. In contrast, Akt, which acts upstream of mTOR, is not affected by HLA-G. The inhibition of SHP-2 by NSC-87877(5 μM), a chemical inhibitor of SHP-2, or the use of siRNA, abrogates dephosphorylation of mTOR and impairs the overexpression of p27 kip in the presence of HLA-G. Together, these results indicate that HLA-G is associated with activation of phosphatase SHP-2, which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry of human-activated T cells.

Original languageEnglish
Article numbere22776
JournalPLoS One
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 24 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Fingerprint Dive into the research topics of 'Lymphocyte cell-cycle inhibition by HLA-G is mediated by phosphatase SHP-2 and acts on the mTOR pathway'. Together they form a unique fingerprint.

Cite this