Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:28028151, PubMed:22461490). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (PubMed:22461490, PubMed:25713392). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (By similarity). Interacts (via DOCKER domain) with GTPase CDC42; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490). The unphosphorylated form interacts (via DOCKER domain) with LRCH1 (via LRR repeats); the interaction prevents the association between DOCK8 and CDC42 (PubMed:28028151). Interacts with CCDC88B (By similarity). Enriched and co-localizes with GTPase CDC42 at the immunological synapse formed during T cell/antigen presenting cell cognate interaction. Translocates from the cytoplasm to the plasma membrane in response to chemokine CXCL12/SDF-1-alpha stimulation. Expressed in T cells (PubMed:28028151). Expressed in bone marrow-derived dendritic cells (PubMed:25713392). The DOCKER domain is necessary and sufficient for the GEF activity. In response to chemokine CXCL12/SDF-1-alpha stimulation, phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation from LRCH1. Strain C3H/HeJ mice harbor a point mutation in Dock8 which results in impaired dendritic cell migration. The mutation is not observed in strains CBA/J, C3H/HeOuJ or C3HeB/FeJ. Mice are viable and fertile (PubMed:22461490). The number of CD4(+) and CD8(+) T-cells are reduced by 50 percent in the spleen and peripheral lymph nodes (PubMed:22461490). The number of marginal zone B cells in the spleen are also reduced (PubMed:22461490). In response to an immune challenge, impaired migration of epidermal dendritic cells to the draining lymph nodes resulting in a failure to prime CD4(+) T-cells characterized by a lack of CD4(+) T-cell proliferation in lymph nodes and a lack of antigen-specific IgG antibody production (PubMed:25713392, PubMed:22461490). Belongs to the DOCK family.