title: Skint-1 is a highly specific, unique selecting component for epidermal T cells.
abstract: αβ T-cell repertoire selection is mediated by peptide-MHC complexes presented by thymic epithelial or myeloid cells, and by lipid-CD1 complexes expressed by thymocytes. γδ T-cell repertoire selection, by contrast, is largely unresolved. Mice mutant for Skint-1, a unique Ig superfamily gene, do not develop canonical Vγ5Vδ1(+) dendritic epidermal T cells. This study shows that transgenic Skint-1, across a broad range of expression levels, precisely and selectively determines the Vγ5Vδ1(+) dendritic epidermal T-cell compartment. Skint-1 is expressed by medullary thymic epithelial cells, and unlike lipid-CD1 complexes, must be expressed by stromal cells to function efficiently. Its unusual transmembrane-cytoplasmic regions severely limit cell surface expression, yet increasing this or, conversely, retaining Skint1 intracellularly markedly compromises function. Each Skint1 domain appears nonredundant, including a unique decamer specifying IgV-domain processing. This investigation of Skint-1 biology points to complex events underpinning the positive selection of an intraepithelial γδ repertoire.
authors.affiliation: London Research Institute, Cancer Research UK, London WC2A 3LY, United Kingdom.
authors.forename: Susannah D
authors.initials: SD
authors.lastname: Barbee
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Woodward
authors.forename: Gleb
authors.initials: G
authors.lastname: Turchinovich
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mention
authors.forename: Julia M
authors.initials: JM
authors.lastname: Lewis
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Boyden
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Robert
authors.initials: R
authors.lastname: Tigelaar
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Hayday
mesh_terms: D000818:Animals; D003713:Dendritic Cells; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D004847:Epithelial Cells; D015870:Gene Expression / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007136:Immunoglobulins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C529023:Skint1 protein, mouse