Mechanics of T Cell Receptor Gene Rearrangement

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2009 Apr 14

PMID 19362456

Citations 133

Authors

Michael S Krangel

Affiliations

Soon will be listed here.

Abstract

The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination signal sequences. They also depend on epigenetic factors. Regulated changes in chromatin structure, directed by enhancers and promoter, can modify the availability of recombination signal sequences to the RAG recombinase. Regulated changes in locus conformation may control the synapsis of distant recombination signal sequences, and regulated changes in subnuclear positioning may influence locus recombination events by unknown mechanisms. Together these influences may explain the ordered activation and inactivation of T cell receptor locus recombination events and the phenomenon of Tcrb allelic exclusion.

Citing Articles

Double-Negative CD4 CD8 Absolute Count Plays a Mediating Role in the Causal Relationship Between Plasma Lipids and Parkinson's Disease: A Mendel Randomized Study.

Wang C, Yuan C Mol Neurobiol. 2025; .

PMID: 39838179 DOI: 10.1007/s12035-025-04691-1.

T-cell Receptor Repertoire Analysis in the Context of Transarterial Chemoembolization Synergy with Systemic Therapy for Hepatocellular Carcinoma.

Li J, Zhang Y, Hu L, Ye H, Yan X, Li X J Clin Transl Hepatol. 2025; 13(1):69-83.

PMID: 39801788 PMC: 11712086. DOI: 10.14218/JCTH.2024.00238.

Harnessing antibody-mediated recognition of the intracellular proteome with T cell receptor-like specificity.

Haus-Cohen M, Reiter Y Front Immunol. 2024; 15():1486721.

PMID: 39650646 PMC: 11621052. DOI: 10.3389/fimmu.2024.1486721.

TCR repertoire dynamics and their responses underscores dengue severity.

Khare K, Yadav S, Tarai B, Budhiraja S, Pandey R iScience. 2024; 27(10):110983.

PMID: 39403197 PMC: 11472631. DOI: 10.1016/j.isci.2024.110983.

Conventional PCR-based versus next-generation sequencing-based approach for T-cell receptor γ gene clonality assessment in mature T-cell lymphomas: A phase 3 diagnostic accuracy study.

Donelli R, Gazzola A, Mannu C, Etebari M, Navari M, Piccaluga P J Biol Methods. 2024; 11(2):e99010013.

PMID: 39323485 PMC: 11423944. DOI: 10.14440/jbm.2024.0002.

References

Drejer-Teel A, Fugmann S, Schatz D . The beyond 12/23 restriction is imposed at the nicking and pairing steps of DNA cleavage during V(D)J recombination. Mol Cell Biol. 2007; 27(18):6288-99. PMC: 2099602. DOI: 10.1128/MCB.00835-07. View

Roldan E, Fuxa M, Chong W, Martinez D, Novatchkova M, Busslinger M . Locus 'decontraction' and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene. Nat Immunol. 2004; 6(1):31-41. PMC: 1592471. DOI: 10.1038/ni1150. View

Skok J, Gisler R, Novatchkova M, Farmer D, de Laat W, Busslinger M . Reversible contraction by looping of the Tcra and Tcrb loci in rearranging thymocytes. Nat Immunol. 2007; 8(4):378-87. DOI: 10.1038/ni1448. View

Jia J, Dai M, Zhuang Y . E proteins are required to activate germline transcription of the TCR Vbeta8.2 gene. Eur J Immunol. 2008; 38(10):2806-20. PMC: 2688731. DOI: 10.1002/eji.200838144. View

Abarrategui I, Krangel M . Regulation of T cell receptor-alpha gene recombination by transcription. Nat Immunol. 2006; 7(10):1109-15. DOI: 10.1038/ni1379. View

Zhao H, Nguyen H, Kang J . Interleukin 15 controls the generation of the restricted T cell receptor repertoire of gamma delta intestinal intraepithelial lymphocytes. Nat Immunol. 2005; 6(12):1263-71. PMC: 2886802. DOI: 10.1038/ni1267. View

Parelho V, Hadjur S, Spivakov M, Leleu M, Sauer S, Gregson H . Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell. 2008; 132(3):422-33. DOI: 10.1016/j.cell.2008.01.011. View

Buch T, Rieux-Laucat F, Forster I, Rajewsky K . Failure of HY-specific thymocytes to escape negative selection by receptor editing. Immunity. 2002; 16(5):707-18. DOI: 10.1016/s1074-7613(02)00312-6. View

Su I, Basavaraj A, Krutchinsky A, Hobert O, Ullrich A, Chait B . Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2002; 4(2):124-31. DOI: 10.1038/ni876. View

10.

McMillan R, Sikes M . Differential activation of dual promoters alters Dbeta2 germline transcription during thymocyte development. J Immunol. 2008; 180(5):3218-28. DOI: 10.4049/jimmunol.180.5.3218. View

11.

Sleckman B, Krangel M . A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation. Immunity. 1999; 10(6):723-33. DOI: 10.1016/s1074-7613(00)80071-0. View

12.

Xiong N, Zhang L, Kang C, Raulet D . Gene placement and competition control T cell receptor gamma variable region gene rearrangement. J Exp Med. 2008; 205(4):929-38. PMC: 2292229. DOI: 10.1084/jem.20071275. View

13.

Schlimgen R, Reddy K, Singh H, Krangel M . Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments. Nat Immunol. 2008; 9(7):802-9. PMC: 2561338. DOI: 10.1038/ni.1624. View

14.

Hayday A, Pennington D . Key factors in the organized chaos of early T cell development. Nat Immunol. 2007; 8(2):137-44. DOI: 10.1038/ni1436. View

15.

Krangel M . Gene segment selection in V(D)J recombination: accessibility and beyond. Nat Immunol. 2003; 4(7):624-30. DOI: 10.1038/ni0703-624. View

16.

Jackson A, Krangel M . Turning T-cell receptor beta recombination on and off: more questions than answers. Immunol Rev. 2006; 209:129-41. DOI: 10.1111/j.0105-2896.2006.00342.x. View

17.

Liu Y, Subrahmanyam R, Chakraborty T, Sen R, Desiderio S . A plant homeodomain in RAG-2 that binds Hypermethylated lysine 4 of histone H3 is necessary for efficient antigen-receptor-gene rearrangement. Immunity. 2007; 27(4):561-71. PMC: 3711682. DOI: 10.1016/j.immuni.2007.09.005. View

18.

Ye S, Maki K, Kitamura T, Sunaga S, Akashi K, Domen J . Induction of germline transcription in the TCRgamma locus by Stat5: implications for accessibility control by the IL-7 receptor. Immunity. 1999; 11(2):213-23. DOI: 10.1016/s1074-7613(00)80096-5. View

19.

Huang C, Sleckman B, Kanagawa O . Revision of T cell receptor {alpha} chain genes is required for normal T lymphocyte development. Proc Natl Acad Sci U S A. 2005; 102(40):14356-61. PMC: 1242309. DOI: 10.1073/pnas.0505564102. View

20.

Agata Y, Katakai T, Ye S, Sugai M, Gonda H, Honjo T . Histone acetylation determines the developmentally regulated accessibility for T cell receptor gamma gene recombination. J Exp Med. 2001; 193(7):873-80. PMC: 2193365. DOI: 10.1084/jem.193.7.873. View