Article abstract
Nature Immunology 8, 835 - 844 (2007)
Published online: 15 July 2007 | Corrected online: 19 October 2007 | doi:10.1038/ni1490
There is a Corrigendum (November 2007) associated with this Article.
Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes
Dimitris Skokos1, Guy Shakhar2,4, Rajat Varma2, Janelle C Waite2, Thomas O Cameron2, Randall L Lindquist1, Tanja Schwickert1, Michel C Nussenzweig1,3,5 & Michael L Dustin2,5
Abstract
T cells survey antigen-presenting dendritic cells (DCs) by migrating through DC networks, arresting and maintaining contact with DCs for several hours after encountering high-potency complexes of peptide and major histocompatibility complex (pMHC), leading to T cell activation. The effects of low-potency pMHC complexes on T cells in vivo, however, are unknown, as is the mechanism controlling T cell arrest. Here we evaluated T cell responses in vivo to high-, medium- and low-potency pMHC complexes and found that regardless of potency, pMHC complexes induced upregulation of CD69, anergy and retention of T cells in lymph nodes. However, only high-potency pMHC complexes expressed by DCs induced calcium-dependent T cell deceleration and calcineurin-dependent anergy. The pMHC complexes of lower potency instead induced T cell anergy by a biochemically distinct process that did not affect T cell dynamics.
- Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA.
- Program in Molecular Pathogenesis and Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
- Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10021, USA.
- Present address: Department of Immunology, Weizmann Institute of Science, Rehovot, 76100, Israel.
- These authors contributed equally to this work.
Correspondence to: Michel C Nussenzweig1,3,5 e-mail: nussen@mail.rockefeller.edu
Correspondence to: Michael L Dustin2,5 e-mail: dustin@saturn.med.nyu.edu
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