title: Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.
abstract: B7 proteins CD80 (B7-1) and CD86 (B7-2) are expressed on most antigen-presenting cells and provide critical co-stimulatory or inhibitory input to T cells via their T-cell-expressed receptors: CD28 and CTLA-4. CD28 is expressed on effector T cells and regulatory T cells (Tregs), and CD28-dependent signals are required for optimum activation of effector T cell functions. CD28 ligation on effector T cells leads to formation of distinct molecular patterns and induction of cytoskeletal rearrangements at the immunological synapse (IS). CD28 plays a critical role in recruitment of protein kinase C (PKC)-θ to the effector T cell IS. CTLA-4 is constitutively expressed on the surface of Tregs, but it is expressed on effector T cells only after activation. As CTLA-4 binds to B7 proteins with significantly higher affinity than CD28, B7 ligand recognition by cells expressing both receptors leads to displacement of CD28 and PKC-θ from the IS. In Tregs, B7 ligand recognition leads to recruitment of CTLA-4 and PKC-η to the IS. CTLA-4 plays a role in regulation of T effector and Treg IS stability and cell motility. Due to their important roles in regulating T-cell-mediated responses, B7 receptors are emerging as important drug targets in oncology. In this review, we present an integrated summary of current knowledge about the role of B7 family receptor-ligand interactions in the regulation of spatial and temporal IS dynamics in effector and Tregs.
authors: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and Immunology Programme, National University of Singapore , Singapore , Singapore.
authors: Joanna
authors: J
authors: Brzostek
authors: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and Immunology Programme, National University of Singapore , Singapore , Singapore.
authors: Nicholas R J
authors: NR
authors: Gascoigne
authors: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and Immunology Programme, National University of Singapore, Singapore, Singapore; Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors: Vasily
authors: V
authors: Rybakin
keywords: CTLA-4; PKC-eta; PKC-theta; Treg; co-inhibition; costimulation; immunological synapse