Genomes and Genes
beta chain t cell antigen receptor gene rearrangement
Summary: Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
- Fukui Y, Hashimoto O, Inayoshi A, Gyotoku T, Sano T, Koga T, et al. Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the presence of a single rearranged T cell receptor beta chain. J Exp Med. 1998;188:897-907 pubmed..Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes. ..
- Levin S, Anderson S, Forbush K, Perlmutter R. A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J. 1993;12:1671-80 pubmed..These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts. ..
- Petrie H, Livak F, Burtrum D, Mazel S. T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production. J Exp Med. 1995;182:121-7 pubmed
- von Boehmer H, Aifantis I, Feinberg J, Lechner O, Saint Ruf C, Walter U, et al. Pleiotropic changes controlled by the pre-T-cell receptor. Curr Opin Immunol. 1999;11:135-42 pubmed..A predominant role is occupied by the pre-TCR, which not only generates large numbers of alphabeta lineage cells but also controls TCRbeta allelic exclusion as well as commitment to the gammadelta lineage versus the alphabeta lineage. ..
- Malissen M, Gillet A, Ardouin L, Bouvier G, Trucy J, Ferrier P, et al. Altered T cell development in mice with a targeted mutation of the CD3-epsilon gene. EMBO J. 1995;14:4641-53 pubmed
- Rodewald H, Kretzschmar K, Takeda S, Hohl C, Dessing M. Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J. 1994;13:4229-40 pubmed
- Guillet M, Brouard S, Gagne K, Sebille F, Cuturi M, Delsuc M, et al. Different qualitative and quantitative regulation of V beta TCR transcripts during early acute allograft rejection and tolerance induction. J Immunol. 2002;168:5088-95 pubmed..In addition, tolerated grafts harbor T cells with a highly altered repertoire, suggestive of self-restricted presentation with some patterns corresponding to previously identified regulatory cells. ..
- Petrie H, Tourigny M, Burtrum D, Livak F. Precursor thymocyte proliferation and differentiation are controlled by signals unrelated to the pre-TCR. J Immunol. 2000;165:3094-8 pubmed..Further, our data suggest that precursor thymocyte differentiation is induced by other, probably ubiquitous, mechanisms that require the presence of normal thymic cellularity, composition, and architecture. ..
- Livak F, Tourigny M, Schatz D, Petrie H. Characterization of TCR gene rearrangements during adult murine T cell development. J Immunol. 1999;162:2575-80 pubmed..Further, because TCR gene rearrangements are generally limited to T lineage cells, these analyses provide molecular evidence that irreversible commitment to the T lineage can occur as early as the CD44highCD25+ stage of development. ..
- Ramiro A, Trigueros C, Marquez C, San Millan J, Toribio M. Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development. J Exp Med. 1996;184:519-30 pubmed
- Burns R, Natarajan K, LoCascio N, O Brien D, Kobori J, Shastri N, et al. Molecular analysis of skewed Tcra-V gene use in T-cell receptor beta-chain transgenic mice. Immunogenetics. 1998;47:107-14 pubmed
- Wang B, Levelt C, Salio M, Zheng D, Sancho J, Liu C, et al. Over-expression of CD3 epsilon transgenes blocks T lymphocyte development. Int Immunol. 1995;7:435-48 pubmed..We therefore speculate that in the homozygous tg epsilon 26 animals the arrest in T cell development was caused by excessive signal transduction events rather than by a toxic effect of the transgenic protein. ..
- Dudley E, Petrie H, Shah L, Owen M, Hayday A. T cell receptor beta chain gene rearrangement and selection during thymocyte development in adult mice. Immunity. 1994;1:83-93 pubmed
- Godfrey D, Kennedy J, Mombaerts P, Tonegawa S, Zlotnik A. Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. J Immunol. 1994;152:4783-92 pubmed
- Casanova J, Cerottini J, Matthes M, Necker A, Gournier H, Barra C, et al. H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J Exp Med. 1992;176:439-47 pubmed
- Mombaerts P, Clarke A, Rudnicki M, Iacomini J, Itohara S, Lafaille J, et al. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992;360:225-31 pubmed..TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta. ..
- Bruggemann M, van der Velden V, Raff T, Droese J, Ritgen M, Pott C, et al. Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia. Leukemia. 2004;18:709-19 pubmed..The assay allowed the detection of one leukemic cell within at least 10(4) polyclonal cells in 93% of cases and will be of high value for future MRD studies. ..
- Williams A, Bland P, Phillips A, Turner S, Brooklyn T, Shaya G, et al. Intestinal alpha beta T cells differentiate and rearrange antigen receptor genes in situ in the human infant. J Immunol. 2004;173:7190-9 pubmed..Thus, mucosal T cell responsiveness to environmental Ag is shaped in situ during early life. ..
- Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano Satoh A, et al. An essential developmental checkpoint for production of the T cell lineage. Science. 2010;329:93-6 pubmed publisher..Our study thus identifies the earliest checkpoint during T cell development and shows that it is Bcl11b-dependent. ..
- Khor B, Mahowald G, Khor K, Sleckman B. Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRbeta locus. Mol Immunol. 2009;46:321-6 pubmed publisher..Our findings demonstrate that cis-acting elements that regulate transcription and accessibility of the TCRbeta locus may functionally overlap with RS sequences, which are known primarily to direct Rag-mediated cleavage. ..
- O Neill H, Jolly C. Germline transcription and expression of Tcrb-V8 genes in peripheral mouse lymphoid tissues. Immunogenetics. 1995;42:309-14 pubmed..The possible function and significance of the expression of a truncated Tcr beta chain is discussed. ..
- Roger T, Boudaly S, Seman M. Negative segregation of Mtv loci in H-2E+ mice selected for high antibody response. Immunogenetics. 1994;40:123-8 pubmed..More importantly, the results suggest that negative segregation of Mtv-encoding Sags contribute to determine the super-responder phenotype of H lines. ..
- Chretien I, Marcuz A, Fellah J, Charlemagne J, Du Pasquier L. The T cell receptor beta genes of Xenopus. Eur J Immunol. 1997;27:763-71 pubmed..The locus is inherited in a diploid manner despite the pseudotetraploidy of the Xenopus laevis and X. gilli used in this study. ..
- Valmori D, Dutoit V, Lienard D, Lejeune F, Speiser D, Rimoldi D, et al. Tetramer-guided analysis of TCR beta-chain usage reveals a large repertoire of melan-A-specific CD8+ T cells in melanoma patients. J Immunol. 2000;165:533-8 pubmed..Together, these results suggest that a large and diverse repertoire of Melan-A-specific T cells using different BV TCR segments is available in A2 melanoma patients. ..
- Veldman C, Gebhard K, Uter W, Wassmuth R, Grötzinger J, Schultz E, et al. T cell recognition of desmoglein 3 peptides in patients with pemphigus vulgaris and healthy individuals. J Immunol. 2004;172:3883-92 pubmed..These findings demonstrate that T cell recognition of distinct Dsg3 peptides is restricted by distinct HLA class II molecules and is independent from the development of pemphigus vulgaris. ..
- Bonnet M, Ferrier P, Spicuglia S. Molecular genetics at the T-cell receptor beta locus: insights into the regulation of V(D)J recombination. Adv Exp Med Biol. 2009;650:116-32 pubmed..In this chapter, we summarize our current knowledge and highlight unanswered questions regarding the regulation of V(D)J recombination at the Tcrb locus, placing emphasis on mouse transgenesis and gene-targeting approaches. ..
- Marodon G, Desjardins D, Mercey L, Baillou C, Parent P, Manuel M, et al. High diversity of the immune repertoire in humanized NOD.SCID.gamma c-/- mice. Eur J Immunol. 2009;39:2136-45 pubmed publisher..Altogether, our results suggest that humanized mice express a diversified repertoire and are able to mount antigen-specific immune responses. ..
- Sun W, Popat U, Hutton G, Zang Y, Krance R, Carrum G, et al. Characteristics of T-cell receptor repertoire and myelin-reactive T cells reconstituted from autologous haematopoietic stem-cell grafts in multiple sclerosis. Brain. 2004;127:996-1008 pubmed..The findings have important implications in the understanding of the role of HSCT as a potential treatment for multiple sclerosis. ..
- Webster G, Onions D, Neil J, Cameron E. Skewed T-cell receptor Vbeta8.2 expression in transgenic CD2-myc induced thymic lymphoma: a role for antigen stimulation in tumour development?. Br J Cancer. 1997;76:739-46 pubmed..The biased TcR usage, together with a mature cell phenotype is consistent with the hypothesis that TcR-mediated signals cooperate with activated myc during T-cell transformation. ..
- Espanhol A, Macedo C, Junta C, Cardoso R, Victorero G, Loriod B, et al. Gene expression profiling during thymus ontogeny and its association with TCRVbeta8.1-Dbeta2.1 rearrangements of inbred mouse strains. Mol Cell Biochem. 2003;252:223-8 pubmed..These data suggest a susceptibility of this strain to expression of MMTV(SW) upon reduction of the rearranged TCRVbeta8.1-Dbeta2.1 segment in developing thymocytes, with parallel IL-7 overexpression. ..
- Simon H, Plötz S, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. 1999;341:1112-20 pubmed..Moreover, the aberrant T cells produced large amounts of interleukin-5 in vitro. Clonal populations of abnormal T cells producing interleukin-5 occur in some patients with idiopathic eosinophilia. ..
- Sim B, Gascoigne N. Reciprocal expression in CD4 or CD8 subsets of different members of the V alpha 11 gene family correlates with sequence polymorphism. J Immunol. 1999;162:3153-9 pubmed..With no apparent restriction in TCR J alpha usage or CDR3 alpha length in C57BL/6, these findings support the idea of V alpha-dependent T cell repertoire selection through preferential recognition of MHC class I or class II molecules. ..
- Lukacher A, Moser J, Hadley A, Altman J. Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection. J Immunol. 1999;163:3369-78 pubmed..Taken together, these findings strongly implicate virus-induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo. ..
- Sebille F, Gagne K, Guillet M, Degauque N, Pallier A, Brouard S, et al. Direct recognition of foreign MHC determinants by naive T cells mobilizes specific Vbeta families without skewing of the complementarity-determining region 3 length distribution. J Immunol. 2001;167:3082-8 pubmed
- Wu C, Bassing C, Jung D, Woodman B, Foy D, Alt F. Dramatically increased rearrangement and peripheral representation of Vbeta14 driven by the 3'Dbeta1 recombination signal sequence. Immunity. 2003;18:75-85 pubmed
- Robins H, Campregher P, Srivastava S, Wacher A, Turtle C, Kahsai O, et al. Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells. Blood. 2009;114:4099-107 pubmed publisher..These methods should prove valuable for assessment of alphabeta T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging. ..
- Wedderburn L, Patel A, Varsani H, Woo P. Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis. Int Immunol. 2001;13:1541-50 pubmed..These data provide powerful data to support the concept that recognition of MHC-peptide complexes by T cells plays a role in the pathogenesis of juvenile arthritis. ..
- Matiasovic J, Andrysikova R, Karasova D, Toman M, Faldyna M. The structure and functional analysis of canine T-cell receptor beta region. Vet Immunol Immunopathol. 2009;132:282-7 pubmed publisher..We identified and analyzed probable structure of canine TCR beta region, which is different when compared to sequences published in GenBank or ENSEMBL databases. ..
- Tripathi R, Jackson A, Krangel M. A change in the structure of Vbeta chromatin associated with TCR beta allelic exclusion. J Immunol. 2002;168:2316-24 pubmed..Hence, the observed changes in Vbeta chromatin structure appear sufficient to account for allelic exclusion of many Vbeta segments. They may contribute to, but not by themselves fully account for, allelic exclusion of others. ..
- Hinton H, Clarke R, Cantrell D. Antigen receptor regulation of phosphoinositide-dependent kinase 1 pathways during thymocyte development. FEBS Lett. 2006;580:5845-50 pubmed..The present data identifying antigen receptor signaling as a key activator of PDK1 mediated signaling afford a molecular explanation for the important role of this molecule in T cells. ..
- Baron V, Bouneaud C, Cumano A, Lim A, Arstila T, Kourilsky P, et al. The repertoires of circulating human CD8(+) central and effector memory T cell subsets are largely distinct. Immunity. 2003;18:193-204 pubmed..Altogether, these observations suggest that most effector memory T cells may not have derived from the central memory subset. ..
- Butler J, Wertz N, Sun J, Sacco R. Comparison of the expressed porcine Vbeta and Jbeta repertoire of thymocytes and peripheral T cells. Immunology. 2005;114:184-93 pubmed..7 usage. These studies show that unlike porcine heavy chain V(H) genes, the occurrence and relative usage of porcine TCR-Vbeta groups resembles that of humans. Thus, highly related gene systems can individually diverge within a species. ..
- Yefenof E, Gafanovitch I, Oron E, Bar M, Klein E. Prophylactic intervention in radiation-leukemia-virus-induced murine lymphoma by the biological response modifier polysaccharide K. Cancer Immunol Immunother. 1995;41:389-96 pubmed..The results suggest that PSK contains a superantigen-like component that selectively activates V beta 8+ T cells. Its administration prelymphoma mice interfered with the process of lymphoma progression...
- Lo J, Zhou H, Fearns C, Reisfeld R, Yang Y, Lee J. Tid1 is required for T cell transition from double-negative 3 to double-positive stages. J Immunol. 2005;174:6105-12 pubmed
- Bonyhadi M, Frohlich M, Rasmussen A, Ferrand C, Grosmaire L, Robinet E, et al. In vitro engagement of CD3 and CD28 corrects T cell defects in chronic lymphocytic leukemia. J Immunol. 2005;174:2366-75 pubmed..Based upon these findings, a clinical trial has been initiated to test the potential therapeutic effects of T cells activated using this approach in patients with CLL. ..
- Zhou J, Dudley M, Rosenberg S, Robbins P. Selective growth, in vitro and in vivo, of individual T cell clones from tumor-infiltrating lymphocytes obtained from patients with melanoma. J Immunol. 2004;173:7622-9 pubmed..A similar analysis may also be useful for monitoring autoimmune responses. ..
- Kasow K, Chen X, Knowles J, Wichlan D, Handgretinger R, Riberdy J. Human CD4+CD25+ regulatory T cells share equally complex and comparable repertoires with CD4+CD25- counterparts. J Immunol. 2004;172:6123-8 pubmed..However, reduced levels of TCR on regulatory T cells suggest different requirements for activation and may contribute to how the immune system regulates whether a particular response is suppressed or augmented. ..
- Pivniouk V, Tsitsikov E, Swinton P, Rathbun G, Alt F, Geha R. Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell. 1998;94:229-38 pubmed..V-D-J rearrangement of the TCRbeta locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes. ..
- Senoo M, Wang L, Suzuki D, Takeda N, Shinkai Y, Habu S. Increase of TCR V beta accessibility within E beta regulatory region influences its recombination frequency but not allelic exclusion. J Immunol. 2003;171:829-35 pubmed..These results provide strong evidence that increase of Vbeta accessibility influences frequency but not allelic exclusion of the TCR Vbeta rearrangement if the Vbeta gene is located in the Ebeta regulatory region. ..
- Klein F, Feldhahn N, Lee S, Wang H, Ciuffi F, von Elstermann M, et al. T lymphoid differentiation in human bone marrow. Proc Natl Acad Sci U S A. 2003;100:6747-52 pubmed..At a frequency <0.5% of mononucleated cells in human bone marrow, this population is rare, yet it exemplifies T lymphoid differentiation in the human already before immigration into the thymus. ..
- Jackson A, Krangel M. Turning T-cell receptor beta recombination on and off: more questions than answers. Immunol Rev. 2006;209:129-41 pubmed..We highlight the many unresolved issues and we discuss how recent concepts emerging from studies of other antigen receptor loci may (or may not) help to resolve these issues. ..
- Van De Wiele C, Marino J, Murray B, Vo S, Whetsell M, Teague T. Thymocytes between the beta-selection and positive selection checkpoints are nonresponsive to IL-7 as assessed by STAT-5 phosphorylation. J Immunol. 2004;172:4235-44 pubmed..This pattern of sensitivity suggests a two-signal mechanism by which survival of thymocytes at these checkpoints is governed. ..
- Direskeneli H, Eksioglu Demiralp E, Kibaroglu A, Yavuz S, Ergun T, Akoglu T. Oligoclonal T cell expansions in patients with Behçet's disease. Clin Exp Immunol. 1999;117:166-70 pubmed..Analysis of the responsible antigens causing the increase in T cell subsets may give insights into the aetiopathogenesis of BD and immunomodulation of these T cells may lead to new treatments. ..