Journal
NATURE GENETICS
Volume 40, Issue 5, Pages 656-662Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.108
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Funding
- Medical Research Council [G0600698B] Funding Source: researchfish
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [R01 CA102703] Funding Source: Medline
- NIAMS NIH HHS [K08 AR002072] Funding Source: Medline
- NICHD NIH HHS [T32 HD007149] Funding Source: Medline
- NIDDK NIH HHS [P30 DK079310] Funding Source: Medline
- Wellcome Trust [071534] Funding Source: Medline
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B cells, alpha beta T cells and gamma delta T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. ab T cells undergo positive selection in the thymus by engagement of their T cell receptors (TCRs) with self-peptides presented by major histocompatibility complex molecules(1). The molecules that select gamma delta T cells are unknown(2-4). V gamma 5(+)V delta 1(+) cells comprise 90% of mouse epidermal gamma delta T cells(4). By mapping and genetic complementation using a strain showing loss of Vc5(+)Vd1(+) cells due to a failure of thymic selection, we show that this defect is caused by mutation in Skint1, a newly identified gene expressed in thymus and skin that encodes a protein with immunoglobulin-like and transmembrane domains. Skint1 is the prototypic member of a rapidly evolving family of at least 11 genes in mouse, with greatest similarity to the butyrophilin genes. These findings define a new family of proteins mediating key epithelial-immune interactions.
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