Pre-TCR signaling components trigger transcriptional activation of a rearranged TCR alpha gene locus and silencing of the pre-TCR alpha locus: implications for intrathymic differentiation.
A rearranged TCR alpha transgene remains transcriptionally inactive in rag-2-/- thymocytes but can be induced by CD3-mediated signals with concomitant maturation of double-negative (DN) thymocytes to the CD4+CD8+ double-positive (DP) stage. Reciprocally, the same signals silence pre-TCR alpha (pT alpha) expression. In normal C57BL/6 thymocytes, TCR alpha expression is not detected in DN thymocytes while, in contrast, TCR beta expression is initiated at the most immature c-kit+CD44+CD25- stage and continues throughout thymocyte development. pT alpha expression is first detected at the intermediate c-kit +/- CD44+CD25+ DN stage, increases during transition to the more mature c-kit-CD44-CD25+ stage and is lost at the DP stage. Thus, although TCR beta and pT alpha expression are independent, the pre-TCR complex mediates signals controlling the appearance of alpha beta TCR through selective regulation of TCR alpha and pT alpha genes.
Koyasu
S
S
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA, USA.
Clayton
L K
LK
Lerner
A
A
Heiken
H
H
Parkes
A
A
Reinherz
E L
EL
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D015533:Transcriptional Activation
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2