Abstract
CLASSICALT lymphocytes recognize foreign antigens in the context of self major histocompatibility complex (MHC) molecules by means of the T-cell receptor (TCR)αβheterodimer1–3. The genes for TCR β -chains, like immunoglobulin genes, are subject to allelic exclusion. The introduction of a functional TCR-β gene into the germline of mice prevents rearrangement of endogenous TCR-β genes4. Here we report that the introduction of a nonfunctional TCR-β gene with a deletion of the major part of the variable region (ΔV-TCR-β), also inhibits endogenous TCR-β gene rearrangement. This inhibition is mediated via the encoded protein because impairment of endogenous TCR-β gene rearrangement is not found if a frameshift mutation is introduced into the DJ region of the ΔV-TCR-β transgene. The Δ V-TCR-β trans-gene can lead to two phenotypes, in which lymphoid development is perturbed. Phenotype A is characterized by a severe impairment of both T and B cell development as reflected by the complete absence of certain lymphoid organs. In phenotype B, lymphoid organs are macroscopically normal, but T cell differentiation is impeded. Virtually all thymocytes lack membrane expression of TCR-αβ, but nevertheless carry the CD4 and CD8 antigens (CD4+CD8+ phenotype); they do not, however, mature further. The defect in mice of phenotype B but not of phenotype A can be corrected by the introduction of a functional TCR-β gene.
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Krimpenfort, P., Ossendorp, F., Borst, J. et al. T cell depletion in transgenic mice carrying a mutant gene for TCR-β. Nature 341, 742–746 (1989). https://doi.org/10.1038/341742a0
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DOI: https://doi.org/10.1038/341742a0
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