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

TY - JOUR

T1 - Skint-1 is a highly specific, unique selecting component for epidermal T cells

AU - Barbee, Susannah D.

AU - Woodward, Martin J.

AU - Turchinovich, Gleb

AU - Mention, Jean-Jacques

AU - Lewis, Julia M.

AU - Boyden, Lynn M.

AU - Lifton, Richard P.

AU - Tigelaar, Robert

AU - Hayday, Adrian C.

PY - 2011/2/22

Y1 - 2011/2/22

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1010890108

DO - 10.1073/pnas.1010890108

M3 - Article

SN - 1091-6490

VL - 108

SP - 3330

EP - 3335

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 8

ER -