| First Author | Ackerknecht M | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 2 | Pages | 520-530 |
| PubMed ID | 28607113 | Mgi Jnum | J:250891 |
| Mgi Id | MGI:6100420 | Doi | 10.4049/jimmunol.1601148 |
| Citation | Ackerknecht M, et al. (2017) Antigen Availability and DOCK2-Driven Motility Govern CD4(+) T Cell Interactions with Dendritic Cells In Vivo. J Immunol 199(2):520-530 |
| abstractText | Parenchymal migration of naive CD4(+) T cells in lymph nodes (LNs) is mediated by the Rac activator DOCK2 and PI3Kgamma 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 PI3Kgamma 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(low) DCs and to find rare pMHC(high) 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. |
