Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal gammadelta T cells.
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.
Boyden
Lynn M
LM
Department of Genetics, Yale University School of Medicine, 333 Cedar St., SHM I-308, New Haven, Connecticut 06510, USA.
Lewis
Julia M
JM
Barbee
Susannah D
SD
Bas
Anna
A
Girardi
Michael
M
Hayday
Adrian C
AC
Tigelaar
Robert E
RE
Lifton
Richard P
RP
D000595:Amino Acid Sequence; D000818:Animals; D018389:Codon, Nonsense; D004817:Epidermis / Q000276:immunology*; D008040:Genetic Linkage; D006239:Haplotypes; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D011487:Protein Conformation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018389:Codon, Nonsense; D007136:Immunoglobulins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C529023:Skint1 protein, mouse