Modulation of immunological synapse by membrane-bound and soluble ligands.
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.
González
Pablo A
PA
Millenniun Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile.
Carreño
Leandro J
LJ
Figueroa
Claudio A
CA
Kalergis
Alexis M
AM
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008024:Ligands; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell