Antigen availability and DOCK2-driven motility govern CD4+ t cell interactions with dendritic cells in vivo

Markus Ackerknecht, Kathrin Gollmer, Philipp Germann, Xenia Ficht, Jun Abe, Yoshinori Fukui, Jim Swoger, Jorge Ripoll, James Sharpe, Jens V. Stein

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Parenchymal migration of naive CD4+ T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kg and is widely assumed to facilitate efficient screening of dendritic cells (DCs) presenting peptide-MHCs (pMHCs). Yet how CD4+ T cell motility, DC density, and pMHC levels interdependently regulate such interactions has not been comprehensively examined. Using intravital imaging of reactive LNs in DC-immunized mice, we show that pMHC levels determined the occurrence and timing of stable CD4+ T cell-DC interactions. Despite the variability in interaction parameters, ensuing CD4+ T cell proliferation was comparable over a wide range of pMHC levels. Unexpectedly, decreased intrinsic motility of DOCK22/2 CD4+ T cells did not impair encounters with DCs in dense paracortical networks and, instead, increased interaction stability, whereas PI3Kg deficiency had no effect on interaction parameters. In contrast, intravital and whole-organ imaging showed that DOCK2-driven T cell motility was required to detach from pMHClow DCs and to find rare pMHChigh DCs. In sum, our data uncover flexible signal integration by scanning CD4+ T cells, suggesting a search strategy evolved to detect low-frequency DCs presenting high cognate pMHC levels.

Original languageEnglish
Pages (from-to)520-530
Number of pages11
JournalJournal of Immunology
Volume199
Issue number2
DOIs
Publication statusPublished - Jul 15 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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