Modulation of immunological synapse by membrane-bound and soluble ligands

• Published in: Cytokine & growth factor reviews Vol. 18; no. 1; pp. 19 - 31
• Main Authors: González, Pablo A, Carreño, Leandro J, Figueroa, Claudio A, Kalergis, Alexis M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2007
• Subjects: Advanced Basic Science; Animals; Antigen Presentation - immunology; Antigen presenting cells; Antigen-Presenting Cells - immunology; Antigens, Neoplasm - immunology; Cell Communication - immunology; Chemokines; Cytokines; Histocompatibility Antigens Class I - immunology; Humans; Immune Tolerance; Immunological synapse; Ligands; Neoplasms - immunology; Peptides - immunology; Receptors, Antigen, T-Cell - immunology; T cell activation; T cells; T-Lymphocytes - immunology; TCR/pMHC interaction kinetics; Immunological synapse; TCR/pMHC interaction kinetics; Cytokines; T cell activation; Antigen presenting cells; T cells; Chemokines
• ISSN: 1359-6101
• DOI: 10.1016/j.cytogfr.2007.01.003

Abstract An efficient adaptive immune response should prevent pathogen infections and tumor growth without causing significant damage to host constituents. A crucial event determining the balance between tolerance and immunity is antigen recognition by T cells on the surface of antigen presenting cells (APC). Several molecular contacts at the interface between T cells and APCs contribute to define the nature of the adaptive immune response against a particular antigen. Upon TCR engagement by a peptide–MHC complex (pMHC) on the surface of an APC, a specialized supra-molecular structure known as immunological synapse (IS) assembles at the interface between these two cells. This structure involves massive re-distribution of membrane proteins, including TCR and pMHC complexes, as well as co-stimulatory and adhesion molecules. Furthermore, IS assembly leads to several important intracellular events necessary for T cell activation, such as recruitment of signaling molecules and cytoskeleton rearrangements. Because IS assembly leads to major consequences on the function of T cells, several studies have attempted to identify both soluble and membrane-bound molecules that could contribute to modulate the IS function. Here we describe recent literature on the regulation of IS assembly and modulation by TCR/pMHC binding kinetics, chemokines and cytokines focusing on their role at controlling the balance between adaptive immunity and tolerance.