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.
journal_name
Proc Natl Acad Sci U S Aauthors
Barbee SD,Woodward MJ,Turchinovich G,Mention JJ,Lewis JM,Boyden LM,Lifton RP,Tigelaar R,Hayday ACdoi
10.1073/pnas.1010890108subject
Has Abstractpub_date
2011-02-22 00:00:00pages
3330-5issue
8eissn
0027-8424issn
1091-6490pii
1010890108journal_volume
108pub_type
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