Antigen Availability and DOCK2-Driven Motility Govern CD4 + T Cell Interactions with Dendritic Cells In Vivo

• Published in: The Journal of immunology (1950) Vol. 199; no. 2; pp. 520 - 530
• Main Authors: Ackerknecht, Markus, Gollmer, Kathrin, Germann, Philipp, Ficht, Xenia, Abe, Jun, Fukui, Yoshinori, Swoger, Jim, Ripoll, Jorge, Sharpe, James, Stein, Jens V
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15-07-2017
• Subjects: Animals; Antigen Presentation; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Communication; Cell interactions; Cell Movement; Cell proliferation; Class Ib Phosphatidylinositol 3-Kinase - deficiency; Class Ib Phosphatidylinositol 3-Kinase - genetics; Class Ib Phosphatidylinositol 3-Kinase - metabolism; Dendritic cells; Dendritic Cells - immunology; GTPase-Activating Proteins - deficiency; GTPase-Activating Proteins - genetics; GTPase-Activating Proteins - metabolism; Histocompatibility Antigens - immunology; Intravital Microscopy - methods; Lymph nodes; Lymph Nodes - immunology; Lymph Nodes - ultrastructure; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Mice; Motility
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601148

Parenchymal migration of naive CD4
T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kγ 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 DOCK2
CD4
T cells did not impair encounters with DCs in dense paracortical networks and, instead, increased interaction stability, whereas PI3Kγ 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 pMHC
DCs and to find rare pMHC
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.