Title

Interleukin 2 Production, Not the Pattern of Early T-cell Antigen Receptor-dependent Tyrosine Phosphorylation, Controls Anergy Induction by Both Agonists and Partial Agonists

Document Type

Article

Publication Date

9-3-1996

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

93

Issue

18

First Page

9736

Last Page

9741

Abstract

Full activation of T cells requires signaling through the T-cell antigen receptor (TCR) and additional surface molecules interacting with ligands on the antigen-presenting cell. TCR recognition of agonist ligands in the absence of accessory signals frequently results in the induction of a state of unresponsiveness termed anergy. However, even in the presence of costimulation, anergy can be induced by TCR partial agonists. The unique pattern of early receptor-induced tyrosine phosphorylation events induced by partial agonists has led to the hypothesis that altered TCR signaling is directly responsible for the development of anergy. Here we show that anergy induction is neither correlated with nor irreversibly determined by the pattern of early TCR-induced phosphorylation. Rather, it appears to result from the absence of downstream events related to interleukin 2 receptor occupancy and/or cell division. This implies that the anergic state can be manipulated independently of the precise pattern of early biochemical changes following TCR occupancy, a finding with implications for understanding the induction of self-tolerance and the use of partial agonist ligands in the treatment of autoimmune diseases.

Notes

Dr. Joaquin Madrenas is currently a faculty member at The University of Western Ontario.