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Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells


B cells, αβ T cells and γδ T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. αβ T cells undergo positive selection in the thymus by engagement of their T cell receptors (TCRs) with self-peptides presented by major histocompatibility complex molecules1. The molecules that select γδ T cells are unknown2,3,4. Vγ5+Vδ1+ cells comprise 90% of mouse epidermal γδ T cells4. By mapping and genetic complementation using a strain showing loss of Vγ5+Vδ1+ 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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Figure 1: Recessive transmission of Vγ5+Vδ1+ T cell deficiency in a B6 × FVBTac F2 cross.
Figure 2: Linkage of Vγ5+Vδ1+ T cell deficiency to chromosome 4.
Figure 3: Skint1 gene and protein structure.
Figure 4: Premature termination codon in Skint1 in FVBTac.
Figure 5: Rescue of Vγ5+Vδ1+ T cell deficiency by a wild-type Skint1 transgene.
Figure 6: Skint1 haplotypes in diverse mouse strains.

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We thank the Yale Transgenic Mouse and Gene Targeting Resource for injection of transgene constructs and E. Boyden, S. Boyden, A. Gharavi and C. Nelson-Williams for helpful discussions. Supported in part by the Howard Hughes Medical Institute, the Wellcome Trust and the US National Institutes of Health.

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Correspondence to Richard P Lifton.

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Boyden, L., Lewis, J., Barbee, S. et al. Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells. Nat Genet 40, 656–662 (2008).

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