Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling.
Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.
Fu
Guo
G
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Vallée
Sébastien
S
Rybakin
Vasily
V
McGuire
Marielena V
MV
Ampudia
Jeanette
J
Brockmeyer
Claudia
C
Salek
Mogjiborahman
M
Fallen
Paul R
PR
Hoerter
John A H
JA
Munshi
Anil
A
Huang
Yina H
YH
Hu
Jianfang
J
Fox
Howard S
HS
Sauer
Karsten
K
Acuto
Oreste
O
Gascoigne
Nicholas R J
NR
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 / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C544192:themis protein, mouse