Deletion of the human T-cell receptor δ-gene by a site-specific recombination

摘要: The newly described T-eell receptor (TCR) δ locus1–5 is located inside the TCR α locus, between variable region (V)α and joining (J)α6,7. Although genes are physically linked on same chromosome, they sequentially expressed during T-cell development8. This implies existence of a highly efficient regulatory mechanism by which these two independently rearranged. We have recently described9 genetic element 'T early (TEA) in humans transcribed foetal thymocytes, spliced alternatively to constant (C)α, TCR- locus (5') group Jα segments (3′). Importantly, TEA flanks common site rearrangement thymus, distinguishes cells using TCR-γ/δ (TEA germline configuration) from TCR-α/β deleted both chromosomes). In order understand this TEA-associated recombination we analysed genomic clones representing thymic rearrangements. show that deletes before productive (VδDδJδ) rearrangement. diversity (D)δ Jδ regions, provide major source gene diversity, eliminated as consequence deletion cannot then be used conjunction with an α-TCR. propose TCR–δ precedes formation α-TCR could down-regulate maturing thymus.