Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection.
T cell antigen receptor (TCR) signaling in CD4(+)CD8(+) double-positive thymocytes determines cell survival and lineage commitment, but the genetic and molecular basis of this process is poorly defined. To address this issue, we used ethylnitrosourea mutagenesis to identify a previously unknown T lineage-specific gene, Themis, which is critical for the completion of positive selection. Themis contains a tandem repeat of a unique globular domain (called 'CABIT' here) that includes a cysteine motif that defines a family of five uncharacterized vertebrate proteins with orthologs in most animal species. Themis-deficient thymocytes showed no substantial impairment in early TCR signaling but did show altered expression of genes involved in the cell cycle and survival before and during positive selection. Our data suggest a unique function for Themis in sustaining positive selection.
Johnson
Andy L
AL
Nuffield Department of Clinical Medicine, Oxford University, UK.
Aravind
L
L
Shulzhenko
Natalia
N
Morgun
Andre
A
Choi
See-Young
SY
Crockford
Tanya L
TL
Lambe
Teresa
T
Domaschenz
Heather
H
Kucharska
Edyta M
EM
Zheng
Lixin
L
Vinuesa
Carola G
CG
Lenardo
Michael J
MJ
Goodnow
Christopher C
CC
Cornall
Richard J
RJ
Schwartz
Ronald H
RH
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005038:Ethylnitrosourea / Q000494:pharmacology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C544192:themis protein, mouse; D005038:Ethylnitrosourea