Skint1, the Prototype of a Newly Identified Immunoglobulin Superfamily Gene Cluster, Positively Selects Epidermal Gammadelta T Cells

Nat Genet. 2008 May;40(5):656-62. doi: 10.1038/ng.108. Epub 2008 Apr 13.

Abstract

B cells, alphabeta T cells and gammadelta T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. alphabeta 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. The molecules that select gammadelta T cells are unknown. Vgamma5+Vdelta1+ cells comprise 90% of mouse epidermal gammadelta T cells. By mapping and genetic complementation using a strain showing loss of Vgamma5+Vdelta1+ 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Codon, Nonsense
  • Epidermis / immunology*
  • Genetic Linkage
  • Haplotypes
  • Immunoglobulins / chemistry
  • Immunoglobulins / genetics*
  • Immunoglobulins / immunology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Multigene Family*
  • Mutation
  • Protein Conformation
  • Receptors, Antigen, T-Cell, gamma-delta / analysis
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Codon, Nonsense
  • Immunoglobulins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Skint1 protein, mouse

Associated data

  • GENBANK/EF494889
  • GENBANK/EF494890
  • GENBANK/EF494891
  • GENBANK/EF494892
  • GENBANK/EF494893
  • GENBANK/EF494894
  • GENBANK/EF494895
  • GENBANK/EF494896
  • GENBANK/EF494897
  • GENBANK/EF494898
  • GENBANK/EF494899
  • GENBANK/EF494900
  • GENBANK/EF494901
  • GENBANK/EF494902
  • GENBANK/EF494903
  • GENBANK/EF494904
  • GENBANK/EF494905
  • GENBANK/EF494906
  • GENBANK/EF494907
  • GENBANK/EU099296
  • GENBANK/EU099297
  • GENBANK/EU099298
  • GENBANK/EU099299
  • GENBANK/EU099300
  • GENBANK/EU099301
  • GENBANK/EU099302
  • GENBANK/EU099303
  • GENBANK/EU099304
  • GENBANK/EU099305
  • GENBANK/EU099306
  • GENBANK/EU099307
  • GENBANK/EU099308
  • GENBANK/EU099309