Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy.
Studies of T cell responses to altered peptide ligands (APLs) have provided functional evidence that a T cell receptor (TCR) can interpret subtle changes in its ligand, resulting in different phenotypic outcomes. One dramatic effect of APL stimulation with live antigen-presenting cells (APCs) is the induction of energy as opposed to proliferation. We investigated the intracellular signaling events involved in generating this unresponsiveness by comparing protein-tyrosine phosphorylation patterns after stimulation with anergy-inducing APL or the immunogenic peptide. In resting T cell clones, presentation with APL/live APC stimulated a unique pattern of TCR phospho-zeta species and a subsequent lack of association with zap70. This demonstrates that the TCR-CD3 complex can engage selective intracellular biochemical signaling pathways as a direct consequence of the nature of the ligand recognized and the initial phosphotyrosine pattern of the TCR-CD3 proteins, leading to different phenotypes.
Sloan-Lancaster
J
J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Shaw
A S
AS
Rothbard
J B
JB
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D017635:Clonal Anergy / Q000276:immunology*; D006454:Hemoglobins / Q000276:immunology; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D006454:Hemoglobins; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; C079201:hemoglobin (64-76); D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse