title: 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.
abstract: T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Stanley
authors.initials: S
authors.lastname: Adoro
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lucas
authors.forename: Sophia D
authors.initials: SD
authors.lastname: Sarafova
authors.forename: Amala S
authors.initials: AS
authors.lastname: Alag
authors.forename: Loretta L
authors.initials: LL
authors.lastname: Doan
authors.forename: Batu
authors.initials: B
authors.lastname: Erman
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liu
authors.forename: Wilfried
authors.initials: W
authors.lastname: Ellmeier
authors.forename: Remy
authors.initials: R
authors.lastname: Bosselut
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D016827:CD8 Antigens; D016207:Cytokines; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell