title: The magnitude of TCR engagement is a critical predictor of T cell anergy or activation.
abstract: Fast dissociation rate of peptide-MHC complexes from TCR has commonly been accepted to cause T cell anergy. In this study, we present evidence that peptides that form transient complexes with HLA-DR1 induce anergy in T cell clones in vitro and specific memory T cells in vivo. We demonstrate that similar to the low densities of long-lived agonist peptide-MHC, short-lived peptide-MHC ligands induce anergy by engagement of approximately 1000 TCR and activation of a similar pattern of intracellular signaling events. These data strongly suggest that short-lived peptides induce anergy by presentation of low densities of peptide-MHC complexes. Moreover, they suggest that the traditional antagonist peptides might also trigger anergy by a similar molecular mechanism. The use of short-lived peptides to induce T cells anergy is a potential strategy for the prevention or treatment of autoimmune diseases.
authors.affiliation: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Saied
authors.initials: S
authors.lastname: Mirshahidi
authors.forename: Laura C Korb
authors.initials: LC
authors.lastname: Ferris
authors.forename: Scheherazade
authors.initials: S
authors.lastname: Sadegh-Nasseri
mesh_terms: D000199:Actins / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002461:Cell Line, Transformed; D017635:Clonal Anergy / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000199:Actins; D015798:HLA-DR1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007376:Interleukin-2; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D013755:Tetradecanoylphorbol Acetate