Signalling events in the anergy induction of T helper 1 cells.

J. Sloan-Lancaster, P. M. Allen

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)189-196; discussion 196-196202
JournalCiba Foundation symposium
StatePublished - 1995


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