TOX: an HMG box protein implicated in the regulation of thymocyte selection.
In the thymus, pre-T cell receptor (pre-TCR)--mediated signaling and then TCR-mediated signaling initiate changes in gene expression that result in the maturation of CD4 and CD8 lineage T cells from common precursors. Using gene chip technology, we isolated a murine gene, designated Tox, that encodes a member of the HMG (high-mobility group) box family of DNA-binding proteins. TOX expression is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not by TCR activation of mature naïve T cells. Transgenic mice that express TOX show expanded CD8+ and reduced CD4+ single positive thymocyte subpopulations. We present evidence here that this phenotype results from a perturbation in lineage commitment due to reduced sensitivity to TCR-mediated signaling. This molecular marker of thymic selection events may therefore play a role in establishing the activation threshold of developing T cells and patterning changes in gene expression.
Wilkinson
Beverley
B
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chen
Jeff Y-F
JY
Han
Peggy
P
Rufner
Kevin M
KM
Goularte
Olivia D
OD
Kaye
Jonathan
J
D000818:Animals; D001483:Base Sequence; D018956:CD5 Antigens / Q000032:analysis; D002454:Cell Differentiation; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D015854:Up-Regulation
D018956:CD5 Antigens; D024002:HMGB Proteins; D011948:Receptors, Antigen, T-Cell