TY - JOUR
T1 - The Magnitude of TCR Engagement is a Critical Predictor of T Cell Anergy or Activation
AU - Mirshahidi, Saied
AU - Korb Ferris, Laura C.
AU - Sadegh-Nasseri, Scheherazade
PY - 2004/5/1
Y1 - 2004/5/1
N2 - 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 ∼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.
AB - 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 ∼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.
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U2 - 10.4049/jimmunol.172.9.5346
DO - 10.4049/jimmunol.172.9.5346
M3 - Article
C2 - 15100274
AN - SCOPUS:2142771839
SN - 0022-1767
VL - 172
SP - 5346
EP - 5355
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -