Signalling events in the anergy induction of T helper 1 cells.
T cells can interact productively with altered peptide ligands (APLs) resulting in different phenotypic outcomes. Stimulation of T helper 1 cells with an APL on live antigen-presenting cells results in the induction of anergy. We investigated the intracellular signalling events involved in generating this anergy by comparing protein tyrosine phosphorylation patterns after stimulation with the anergy-inducing APL or the immunogenic peptide. Stimulation by an APL resulted in a unique pattern of T cell receptor (TCR) phospho-zeta species, which was not observed with any dose of immunogenic peptide. This altered phospho-zeta pattern had a profound functional significance, in that the tyrosine kinase ZAP-70 was not activated. Thus, anergy can be induced by changing the constellation of intracellular signalling events in a T cell. These findings demonstrate that the TCR-CD3 complex can engage selective intracellular biochemical signalling pathways as a direct consequence of the nature of the ligand recognized and the initial phosphotyrosine pattern of the TCR-CD3 proteins. This then leads to different phenotypes.
Sloan-Lancaster
J
J
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Allen
P M
PM
D017635:Clonal Anergy; D006801:Humans; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*
D017260:Receptor-CD3 Complex, Antigen, T-Cell