TCR-delta gene rearrangement and selection during fetal thymocyte development.
TCR delta-chain gene rearrangements were analyzed at different stages of thymic ontogeny. The VDJ delta junctional sequences of the dominantly expressed TCR delta-chain V7 subfamily are highly conserved in fetal and neonatal thymocytes. They are equally conserved in C delta-targeted mice lacking cell surface expression of gamma delta receptors, indicating evolutionary selection acting at the level of DNA rearrangement. Yet, in C delta-mutant mice, the frequency of in-frame transcripts is reduced to 61%, from 88% in wild-type mice, suggesting cellular selection of this DV7-overexpressing gamma delta thymocyte subset. In contrast, in genomic DNA rearrangements, no difference was found in the frequency of productive rearrangements between mutant (26%) and wild-type mice (31%). This in-frame rate, characteristic of random rearrangements, indicates that positive selection is not required for thymic maturation of gamma delta T cells. The results are discussed with regard to models of alpha beta/gamma delta lineage commitment.
Wilbert
O M
OM
Department of Immunology, Paul Ehrlich Institute, Langen, Germany.
Weber-Arden
J
J
Kabelitz
D
D
Arden
B
B
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005314:Embryonic and Fetal Development / Q000235:genetics* / Q000276:immunology*; D019143:Evolution, Molecular; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000502:physiology*; D005799:Genes, Dominant / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*
D016692:Receptors, Antigen, T-Cell, gamma-delta