Essential role of the pre-T cell receptor in allelic exclusion of the T cell receptor beta locus.
Following the recent realization that TCR beta transgenes can severely inhibit the rearrangement of endogenous Vbeta gene segments in the absence of pre-TCR alpha (pT alpha) chains, we tested whether the pre-TCR has an essential role in TCR beta allelic exclusion under more physiological conditions by analyzing TCR rearrangement in immature thymocytes by single-cell PCR. Our results in pT alpha+ mice are consistent with an ordered model of TCR beta rearrangement beginning on one allele and continuing on the other only when the first attempt is unsuccessful. By contrast, a higher proportion of thymocytes from pT alpha-/- mice exhibited two productive TCR beta alleles. Thus, the pre-TCR-independent suppression of rearrangement by TCR beta transgenes represents a transgene artifact, whereas under physiological conditions the pre-TCR is essential for allelic exclusion.
Aifantis
I
I
Institut Necker, Institut National de la Santé et Recherche Medicale, 373, Paris, France.
Buer
J
J
von Boehmer
H
H
Azogui
O
O
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction / Q000379:methods; D011499:Protein Processing, Post-Translational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*
D016693:Receptors, Antigen, T-Cell, alpha-beta