scholarly journals T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1472-1483 ◽  
Author(s):  
A Bonati ◽  
P Zanelli ◽  
S Ferrari ◽  
A Plebani ◽  
B Starcich ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Transcript ◽  
Beta Chain ◽  
Early Stages ◽  
Human Thymus ◽  
Nucleotide Insertions ◽  
Beta Gene

Abstract T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

scholarly journals T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1472-1483 ◽  
Author(s):  
A Bonati ◽  
P Zanelli ◽  
S Ferrari ◽  
A Plebani ◽  
B Starcich ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Transcript ◽  
Beta Chain ◽  
Early Stages ◽  
Human Thymus ◽  
Nucleotide Insertions ◽  
Beta Gene

T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

scholarly journals Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.

1986 ◽  
Vol 163 (2) ◽  
pp. 383-399 ◽  
Author(s):  
R F Jarrett ◽  
H Mitsuya ◽  
D L Mann ◽  
J Cossman ◽  
S Broder ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Function ◽  
Tumor Cells ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Primary Tumor ◽  
Gene Rearrangement ◽  
Cell Receptor ◽  
Beta Chain ◽  
Beta Gene

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.

scholarly journals p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene.

1993 ◽  
Vol 90 (7) ◽  
pp. 2685-2689 ◽  
Author(s):  
H. Messier ◽  
T. Fuller ◽  
S. Mangal ◽  
H. Brickner ◽  
S. Igarashi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

scholarly journals Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development.

1996 ◽  
Vol 184 (2) ◽  
pp. 519-530 ◽  
Author(s):  
A R Ramiro ◽  
C Trigueros ◽  
C Márquez ◽  
J L San Millán ◽  
M L Toribio
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Development ◽  
Cell Receptor ◽  
Beta Chain ◽  
Thymocyte Development ◽  
Gene Encoding ◽  
Thymic Development ◽  
Alpha Beta ◽  
Beta Gene

In murine T cell development, early thymocytes that productively rearrange the T cell receptor (TCR) beta locus are selected to continue maturation, before TCR alpha expression, by means of a pre-TCR alpha- (pT alpha-) TCR beta heterodimer (pre-TCR). The aim of this study was to identify equivalent stages in human thymocyte development. We show here that variable-diversity-joining region TCR beta rearrangement and the expression of full-length TCR beta transcripts have been initiated in some immature thymocytes at the TCR alpha/beta- CD4+CD8- stage, and become common in a downstream subset of TCR alpha/beta- CD4+CD8+ thymocytes that is highly enriched in large cycling cells. TCR beta chain expression was hardly detected in TCR alpha/beta- CD4+CD8- thymocytes, whereas cytoplasmic TCR beta chain was found in virtually all TCR alpha/beta- CD4+CD8+ blasts. In addition, a TCR beta complex distinct from the mature TCR alpha/beta heterodimer was immunoprecipitated only from the latter subset. cDNA derived from TCR alpha/beta- CD4+CD8+ blasts allowed us to identify and clone the gene encoding the human pT alpha chain, and to examine its expression at different stages of thymocyte development. Our results show that high pT alpha transcription occurs only in CD4+CD8- and CD4+CD8+ TCR alpha/beta- thymocytes, whereas it is weaker in earlier and later stages of development. Based on these results, we propose that the transition from TCR alpha/beta- CD4+CD8- to TCR alpha/beta- CD4+CD8+ thymocytes represents a critical developmental stage at which the successful expression of TCR beta promotes the clonal expansion and further maturation of human thymocytes, independent of TCR alpha.

scholarly journals A Ki-1 (CD30)-positive human cell line (Karpas 299) established from a high-grade non-Hodgkin's lymphoma, showing a 2;5 translocation and rearrangement of the T-cell receptor beta-chain gene

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 234-240 ◽  
Author(s):  
P Fischer ◽  
E Nacheva ◽  
DY Mason ◽  
PD Sherrington ◽  
C Hoyle ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Human Cell Line ◽  
Chain Gene ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Blast Cells ◽  
Receptor Beta

We describe the characterization of a new human cell line, Karpas 299 (K299), established from blast cells in the peripheral blood of a 25- year-old white man. His illness, which began with enlarged occipital and axillary nodes and weight loss, ended after 7 months with generalized lymphadenopathy, pleural effusion, and bone marrow involvement. A lymph node biopsy showed a large cell lymphoma mainly sinusoidal in distribution. The blast cells with pleomorphic nuclei resembled primitive histiocytes. The cells, which expressed the T-cell- associated markers CD4 and CD5, were positive for HLA-DR, epithelial membrane antigen, and CD30 (Ki-1 antigen). The karyotype was aneuploid and included a translocation 2;5. The site of translocation on chromosome 5 (at 5q35.1) is in the region of the locus of the c-fms oncogene (receptor of the monocyte-macrophage colony-stimulating factor MCSF or CSF-1). The cell line Karpas 299 has the same karyotype and pattern of antigen expression as the patient's cells. Northern blot analysis of RNA showed an active rearrangement of the T-cell receptor beta-chain gene. This is to our knowledge the first Ki-1 antigen- positive line to be established from a case of non-Hodgkin's lymphoma.

Regulation of T-cell receptor beta-chain gene assembly by recombination signals: the beyond 12/23 restriction

2004 ◽  
Vol 200 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Robert E. Tillman ◽  
Andrea L. Wooley ◽  
Maureen M. Hughes ◽  
Bernard Khor ◽  
Barry P. Sleckman
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Beta Chain ◽  
Gene Assembly ◽  
T Cell Receptor Beta ◽  
Receptor Beta

scholarly journals The contribution of NZW genes to lupus-like disease in (NZB x NZW)F1 mice.

1987 ◽  
Vol 165 (5) ◽  
pp. 1237-1251 ◽  
Author(s):  
B L Kotzin ◽  
E Palmer
Keyword(s):  
T Cell ◽  
Renal Disease ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Complex ◽  
Beta Chain ◽  
Autoantibody Production ◽  
Severe Renal Disease ◽  
Cell Receptor Alpha

Unlike parental NZB or NZW mice, (NZB X NZW)F1 mice exhibit a lupus-like disease characterized by high serum levels of IgG antinuclear antibodies and a fatal immune-complex glomerulonephritis. At least three unlinked gene loci can be distinguished in NZW mice that conceivably contribute to a T cell-dependent autoimmune disease, including the MHC (H-2z) and the T cell receptor alpha and beta chain gene complexes. We undertook an (NZB X NZW)F1 X NZB backcross to determine the relative contribution of these NZW genes to lupus-like renal disease and autoantibody production in F1 mice. The incidence of severe renal disease and elevated levels of IgG antibodies to dsDNA and histone in the backcross mice was approximately half of that observed in (NZB X NZW)F1 mice. Furthermore, there was a strong correlation between the presence of the NZW H-2z haplotype and lupus-like disease in backcross mice. Approximately 90% of backcross mice with disease carried the NZW H-2z locus compared with 16% of mice without disease; nearly 90% of H-2d/z mice expressed severe autoimmune disease. In contrast, no association was apparent between the presence of the NZW T cell receptor alpha chain gene complex or beta chain gene complex and severe renal disease or autoantibody production. Thus, the NZW MHC or gene(s) linked to this locus appear to be the only dominant NZW genetic contribution to F1 disease.

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