title: Fine tuning of the threshold of T cell selection by the Nck adapters.
abstract: Thymic selection shapes the T cell repertoire to ensure maximal antigenic coverage against pathogens while preventing autoimmunity. Recognition of self-peptides in the context of peptide-MHC complexes by the TCR is central to this process, which remains partially understood at the molecular level. In this study we provide genetic evidence that the Nck adapter proteins are essential for thymic selection. In vivo Nck deletion resulted in a reduction of the thymic cellularity, defective positive selection of low-avidity T cells, and impaired deletion of thymocytes engaged by low-potency stimuli. Nck-deficient thymocytes were characterized by reduced ERK activation, particularly pronounced in mature single positive thymocytes. Taken together, our findings identify a crucial role for the Nck adapters in enhancing TCR signal strength, thereby fine-tuning the threshold of thymocyte selection and shaping the preimmune T cell repertoire.
authors.affiliation: INSERM, Curie Institute, Paris, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Roy
authors.forename: Dieudonnée
authors.initials: D
authors.lastname: Togbe
authors.forename: Amy
authors.initials: A
authors.lastname: Holdorf
authors.forename: Dmitry
authors.initials: D
authors.lastname: Trubetskoy
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nabti
authors.forename: Günter
authors.initials: G
authors.lastname: Küblbeck
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmitt
authors.forename: Annette
authors.initials: A
authors.lastname: Kopp-Schneider
authors.forename: Frank
authors.initials: F
authors.lastname: Leithäuser
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Bladt
authors.forename: Günter J
authors.initials: GJ
authors.lastname: Hämmerling
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Anna
authors.initials: A
authors.lastname: Tafuri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017353:Gene Deletion; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006649:Histocompatibility Antigens; C078332:Nck protein; D015513:Oncogene Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D048049:Extracellular Signal-Regulated MAP Kinases