Junctional diversity in signal joints from T cell receptor beta and delta loci via terminal deoxynucleotidyl transferase and exonucleolytic activity.
The site-specific V(D)J recombination reaction necessary to assemble the genes coding for immunoglobulin (Ig) and T cell receptor (TCR) variable regions is initiated by a precise double strand cut at the border of the recombination signals flanking the genes. Extensive processing of the coding ends before their ligation accounts for most of the Ig and TCR repertoire diversity. This processing includes both base additions to and loss from the coding ends. On the other hand, it has generally been thought that signal ends are not modified before they are fused, and that signal joints consist of a perfect head-to-head ligation of the recombination signals. In this study, we analyzed signal joints created during the rearrangement of different TCR-beta and TCR-delta genes in thymocytes. We show that a significant fraction (up to 24%) of these signal joints exhibits junctional diversity. This diversity results from N nucleotide additions for TCR-beta signal joints, and from N additions and exonucleolytic digestion for TCR-delta joints. Altogether, our findings suggest that: (a) signal ends can undergo some of the same modifications as coding ends, (b) inversional rearrangement generates more diversity than deletional events, and (c) fine differences exist in the recombinase/DNA complexes formed at each rearranging locus.
Candéias
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SAIC Frederick, National Cancer Institute (NCI)-Frederick Cancer Research Center, Maryland 21702-1201, USA.
Muegge
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Durum
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D000818:Animals; D000831:Animals, Newborn; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D014644:Genetic Variation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D011995:Recombination, Genetic; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology
D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004253:DNA Nucleotidylexotransferase; D005090:Exodeoxyribonucleases