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

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

Author information

  • 1London Research Institute, Cancer Research UK, London WC2A 3LY, United Kingdom.

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.

PMID:
21300860
[PubMed - indexed for MEDLINE]
PMCID:
PMC3044407
Free PMC Article

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