T cell receptor δ gene mutant mice: Independent generation of αβ T cells and programmed rearrangements of γδ TCR genes

Abstract

T cells bearing T cell receptor (TCR) γ and δ chain heterodimers are first generated early in ontogeny. They form distinct subsets that differ in their TCR repertoires and tissue distribution. Disruption of the mouse TCR Cδ gene segment by a gene targeting method caused the complete loss of T cells bearing TCR γδ chains, but had little or no effect on the development of T cells bearing TCR αβ chains. The analyses of TCR γ and δ genes in the mutant mice suggest that intracellular mechanisms acting at the level of DNA rearrangement play key roles in the differential γ and δ gene rearrangements and in the generation of the highly restricted junctional sequences during fetal thymic development.