title: Increased mobility of major histocompatibility complex I-peptide complexes decreases the sensitivity of antigen recognition.
abstract: CD8(+) cytotoxic T lymphocytes (CTL) can recognize and kill target cells expressing only a few cognate major histocompatibility complex (MHC) I-peptide complexes. This high sensitivity requires efficient scanning of a vast number of highly diverse MHC I-peptide complexes by the T cell receptor in the contact site of transient conjugates formed mainly by nonspecific interactions of ICAM-1 and LFA-1. Tracking of single H-2K(d) molecules loaded with fluorescent peptides on target cells and nascent conjugates with CTL showed dynamic transitions between states of free diffusion and immobility. The immobilizations were explained by association of MHC I-peptide complexes with ICAM-1 and strongly increased their local concentration in cell adhesion sites and hence their scanning by T cell receptor. In nascent immunological synapses cognate complexes became immobile, whereas noncognate ones diffused out again. Interfering with this mobility modulation-based concentration and sorting of MHC I-peptide complexes strongly impaired the sensitivity of antigen recognition by CTL, demonstrating that it constitutes a new basic aspect of antigen presentation by MHC I molecules.
authors.affiliation: Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Jean-Manuel
authors.initials: JM
authors.lastname: Segura
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Silke
authors.initials: S
authors.lastname: Mark
authors.forename: Danijel
authors.initials: D
authors.lastname: Dojcinovic
authors.forename: Alexandre
authors.initials: A
authors.lastname: Johannsen
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bosshard
authors.forename: Georgi
authors.initials: G
authors.lastname: Angelov
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Legler
authors.forename: Horst
authors.initials: H
authors.lastname: Vogel
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007739:L Cells; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; C024755:H-2K(K) antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1