Skint-1 is a highly specific, unique selecting component for epidermal T cells

Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3330-5. doi: 10.1073/pnas.1010890108. Epub 2011 Feb 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells
  • Epidermal Cells
  • Epidermis / immunology*
  • Epithelial Cells
  • Gene Expression / immunology
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocyte Subsets
  • T-Lymphocytes / immunology*

Substances

  • Immunoglobulins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Skint1 protein, mouse