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

Susannah D. Barbee, Martin J. Woodward, Gleb Turchinovich, Jean-Jacques Mention, Julia M. Lewis, Lynn M. Boyden, Richard P. Lifton, Robert Tigelaar, Adrian C. Hayday

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

alpha beta 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. gamma delta T-cell repertoire selection, by contrast, is largely unresolved. Mice mutant for Skint-1, a unique Ig superfamily gene, do not develop canonical V gamma 5V delta 1(+) dendritic epidermal T cells. This study shows that transgenic Skint-1, across a broad range of expression levels, precisely and selectively determines the V gamma 5V delta 1(+) 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 Skint-1 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 gamma delta repertoire.
Original languageEnglish
Pages (from-to)3330 - 3335
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number8
DOIs
Publication statusPublished - 22 Feb 2011

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