Con A activates an Akt/PKB dependent survival mechanism to modulate TCR induced cell death in double positive thymocytes

Judit Pongracz, Sonia Parnell, Graham Anderson, Jean Pierre Jaffrézou, Eric Jenkinson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

While low avidity ligation of the T cell receptor (TCR) leads to positive selection and further maturation of developing thymocytes providing the immune system with mature CD4+ and CD8+ (single positive) T cells, high avidity ligation triggers negative selection by apoptotic cell death and therefore the TCR repertoire is purged of autoreactive T cells. On peripheral T cells, however, high avidity ligation of the TCR triggers activation and survival not death. In the present study we used concanavalin A (Con A) and α-CD3ε antibody to investigate a possible survival mechanism in connection with TCR ligation. Con A and α-CD3ε were used in the study for the following reasons: (1) they both mimic the effects of high avidity TCR ligation by activating peripheral T cells, and (2) they trigger distinctively different physiological changes in developing thymocytes. While Con A supports events associated with cellular survival, α-CD3ε induces apoptotic cell death. In our experimental system the TCR was cross-linked by Con A and α-CD3ε in thymocytes of major histocompatibility complex (MHC) deficient thymus organ cultures, where signals from the TCR can be triggered on zero background signal level. We have found that TCR cross-linking by Con A and not by α-CD3ε decreases the gene and protein expression of the pro-apoptotic molecule, Bad; and that Con A is capable of the activation of the survival signalling pathway including protein kinase B (Akt/PKB) independently of phosphatidyl inositol kinase (PI3K).

Original languageEnglish
Pages (from-to)1013-1023
Number of pages11
JournalMolecular Immunology
Volume39
Issue number16
DOIs
Publication statusPublished - Jun 2003

Keywords

  • Akt/PKB
  • Con A
  • Thymocytes

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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