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

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.