Raising the threshold for T-cell activation

Abstract

Researchers at the La Jolla Institute for Allergy and Immunology have reported recently on how lymphocytes set the threshold for deciding between responding to a challenge or remaining quiescent, following activation through the T-cell antigen receptor and the CD28 costimulatory receptor. They report that PI 3-K, a key enzyme involved in optimal T-cell activation, is ubiquinated by an inhibitory protein called Cbl-b. Normally, Cbl-b marks proteins for destruction within cells; however, its interaction with the antigen and costimulatory receptors is different. Instead of initiating the pathway to remove proteins, the interaction of Cbl-b with PI 3-K blocks the recruitment of PI 3-K to cell-surface receptors, making it more difficult to activate lymphocytes and, therefore, raising the threshold for activation. Nat. Immunol. (2001) 2, 870–875 SW