Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes.
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.
Skokos
Dimitris
D
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA.
Shakhar
Guy
G
Varma
Rajat
R
Waite
Janelle C
JC
Cameron
Thomas O
TO
Lindquist
Randall L
RL
Schwickert
Tanja
T
Nussenzweig
Michel C
MC
Dustin
Michael L
ML
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D010455:Peptides