دورية أكاديمية
Differential utilization of T cell receptor TCR alpha/TCR delta locus variable region gene segments is mediated by accessibility.
| العنوان: | Differential utilization of T cell receptor TCR alpha/TCR delta locus variable region gene segments is mediated by accessibility. |
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| المؤلفون: | Lee YN; Howard Hughes Medical Institute, Children's Hospital Boston, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA., Alt FW, Reyes J, Gleason M, Zarrin AA, Jung D |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2009 Oct 13; Vol. 106 (41), pp. 17487-92. Date of Electronic Publication: 2009 Sep 28. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Genes, T-Cell Receptor alpha/*genetics , Genes, T-Cell Receptor delta/*genetics , Immunoglobulin Variable Region/*genetics, Animals ; Blotting, Southern ; Chimera/genetics ; Gene Rearrangement ; Germ-Line Mutation ; Mice ; Plasmids ; Recombination, Genetic ; Restriction Mapping ; VDJ Recombinases/genetics |
| مستخلص: | T cell receptor (TCR) variable region exons are assembled from germline V, (D), and J gene segments, each of which is flanked by recombination signal (RS) sequences that are composed of a conserved heptamer, a spacer of 12 or 23 bp, and a characteristic nonamer. V(D)J recombination only occurs between V, D, and J segments flanked by RS sequences that contain, respectively, 12(12-RS)- and 23(23-RS)-bp spacers (12/23 rule). Additional mechanisms can restrict joining of 12/23 RS matched segments beyond the 12/23 rule (B12/23). The TCRdelta locus is contained within the TCRalpha locus; TCRalpha variable region exons are encoded by TRAV and TRAJ segments and those of TCRdelta by TRDV, TRDD, and TRDJ segments. On the basis of the 12/23 rule, both TRAV and TRDV gene segments are compatible to rearrange with TRDD gene segments; however, TRAV-to-TRDD joins are not observed in vivo. Absence of TRAV-to-TRDD rearrangement might be explained either by B12/23 restriction or by differential accessibility of the TRDV versus TRAV gene segments for rearrangement to TRDD. We used in vitro substrate analysis to reveal that both TRAV and TRDV 23-RSs mediate rearrangements to the 5'TRDD1 12-RS, demonstrating that B12/23 restriction does not explain these rearrangement biases. However, targeted replacement of TRDD1 and its 12-RSs with TRAJ38 and its 12-RS showed that TRDV gene segments rearrange with the ectopic TRAJ38, whereas TRAV segments do not. Our results demonstrate that sorting of TRAV and TRDV gene segments is determined by differential locus accessibility during T cell development. |
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| معلومات مُعتمدة: | R01 AI020047 United States AI NIAID NIH HHS; R01 AI020047-28 United States AI NIAID NIH HHS; R37 AI020047 United States AI NIAID NIH HHS; AI-20047 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Immunoglobulin Variable Region) EC 2.7.7.- (VDJ Recombinases) |
| تواريخ الأحداث: | Date Created: 20091007 Date Completed: 20091103 Latest Revision: 20240418 |
| رمز التحديث: | 20240418 |
| مُعرف محوري في PubMed: | PMC2765100 |
| DOI: | 10.1073/pnas.0909723106 |
| PMID: | 19805067 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.0909723106 |