From Dendrite to Dendritic

Abstract

Naïve T cell activation by dendritic cells (DCs) is a critical step in the adaptive immune response. Activation occurs as a result of prolonged contact between the cells through the formation of an immunological synapse (IS). The IS involves interactions between peptide major histocompatibility complexes (pMHCs) on the DC and T cell receptor (TCR) complexes on the naïve cell and between adhesion molecules on both cells. Although much is known about the cytoplasmic events that occur in T cells during IS formation, little is known about what occurs in DCs. Bloom et al . hypothesized that molecules involved in the formation of neuronal synapses might also play a role in IS formation. Immunofluorescence studies showed that the scaffold protein spinophilin, well known for its role in neuronal dendritic spines, was present in the cytoplasm of immature mouse DCs but was colocalized with MHC at the plasma membrane of mature DCs. When mature DCs that expressed a fusion protein of spinophilin and green fluorescent protein (GFP) were cocultured with antigen-specific T cells in the presence of antigen, live confocal microscopy showed that spinophilin-GFP was quickly distributed to the plasma membrane at the side of the DC closest to TCR clusters in the T cells. Antigen-specific T cells transferred to spinophilin-deficient mice were less efficiently activated than were those transferred to wild-type mice. Lack of spinophilin had no effect on MHC localization or on antigen uptake. This study provides a glimpse into the DC during IS formation and suggests that spinophilin is important for efficient antigen presentation to T cells. As Seed and Xavier discuss, this study raises important new questions about what other partners spinophilin might have. O. Bloom, J. J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, I. Mellman, Spinophilin participates in information transfer at immunological synapses. J . Cell Biol . 181 , 203-211 (2008). [Abstract] [Full Text] B. Seed, R. Xavier, Spinophilin and the immune synapse. J . Cell Biol . 181 , 181-183 (2008). [Abstract] [Full Text]