scholarly journals Rearrangement and expression of T-cell receptor delta genes in T-cell acute lymphoblastic leukemias

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 334-342 ◽  
Author(s):  
JJ van Dongen ◽  
IL Wolvers-Tettero ◽  
F Wassenaar ◽  
J Borst ◽  
P van den Elsen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Receptor Expression ◽  
The Other ◽  
Gamma Delta ◽  
Delta Gene ◽  
Gene Transcripts ◽  
Alpha Beta

Abstract We have analyzed T-cell receptor delta (TcR-delta) gene rearrangement and transcription in appropriately phenotyped mononuclear cells derived from 12 patients with T-cell acute lymphoblastic leukemia (T-ALL). The T-ALL cells were also analyzed for rearrangement and transcription of the T-cell receptor(TcR)-beta and gamma genes as well as for the presence of TcR-alpha gene transcripts. Four T-ALLs expressed TcR-gamma delta at the cell surface, while three expressed TcR-alpha beta. The other five T-ALLs did not express a TcR-CD3 complex on their cell membrane. The TcR-gamma delta + T-ALL had rearranged both TcR-delta gene alleles and contained mature 2.2 and 1.5 kb TcR-delta transcripts. In one case, immature 1.9 and 1.2 kb TcR-delta transcripts were also found. Furthermore they contained mature TcR-gamma mRNA, mature or immature TcR-beta mRNA, but no TcR-alpha mRNA. The three TcR-alpha beta + T-ALLs contained mature alpha and beta transcripts, but lacked TcR- delta transcripts as a result of deletion of both TcR-delta gene alleles. These data are in line with a mutually exclusive expression of TcR-alpha and -delta genes, which may be important to ensure the presence of only one type of TcR per T cell. One of the five CD3- T- ALLs had germline TcR-beta, gamma, and delta genes. The other four CD3- T-ALLs had rearranged their TcR-beta, gamma, and delta genes and contained immature 1.9 and 1.2 kb TcR-delta gene transcripts. Remarkably, one of these T-ALLs also contained TcR-alpha transcripts in addition to the immature TcR-delta transcripts, which was in line with the deletion of one TcR-delta gene allele and rearrangement of the other allele. This suggests that prevention of dual receptor expression may not only be regulated by the presence of germline TcR-alpha genes in TcR-gamma delta + cells or by deletion of both TcR-delta gene alleles in TcR-alpha beta + cells, but also via other regulation mechanisms. Finally, our data indicated that the combinatorial repertoire of the TcR-delta genes is limited, which has also been described for the TcR-gamma genes.

scholarly journals Rearrangement and expression of T-cell receptor delta genes in T-cell acute lymphoblastic leukemias

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 334-342
Author(s):  
JJ van Dongen ◽  
IL Wolvers-Tettero ◽  
F Wassenaar ◽  
J Borst ◽  
P van den Elsen
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Cell Receptor ◽  
Receptor Expression ◽  
The Other ◽  
Gamma Delta ◽  
Delta Gene ◽  
Gene Transcripts ◽  
Alpha Beta

We have analyzed T-cell receptor delta (TcR-delta) gene rearrangement and transcription in appropriately phenotyped mononuclear cells derived from 12 patients with T-cell acute lymphoblastic leukemia (T-ALL). The T-ALL cells were also analyzed for rearrangement and transcription of the T-cell receptor(TcR)-beta and gamma genes as well as for the presence of TcR-alpha gene transcripts. Four T-ALLs expressed TcR-gamma delta at the cell surface, while three expressed TcR-alpha beta. The other five T-ALLs did not express a TcR-CD3 complex on their cell membrane. The TcR-gamma delta + T-ALL had rearranged both TcR-delta gene alleles and contained mature 2.2 and 1.5 kb TcR-delta transcripts. In one case, immature 1.9 and 1.2 kb TcR-delta transcripts were also found. Furthermore they contained mature TcR-gamma mRNA, mature or immature TcR-beta mRNA, but no TcR-alpha mRNA. The three TcR-alpha beta + T-ALLs contained mature alpha and beta transcripts, but lacked TcR- delta transcripts as a result of deletion of both TcR-delta gene alleles. These data are in line with a mutually exclusive expression of TcR-alpha and -delta genes, which may be important to ensure the presence of only one type of TcR per T cell. One of the five CD3- T- ALLs had germline TcR-beta, gamma, and delta genes. The other four CD3- T-ALLs had rearranged their TcR-beta, gamma, and delta genes and contained immature 1.9 and 1.2 kb TcR-delta gene transcripts. Remarkably, one of these T-ALLs also contained TcR-alpha transcripts in addition to the immature TcR-delta transcripts, which was in line with the deletion of one TcR-delta gene allele and rearrangement of the other allele. This suggests that prevention of dual receptor expression may not only be regulated by the presence of germline TcR-alpha genes in TcR-gamma delta + cells or by deletion of both TcR-delta gene alleles in TcR-alpha beta + cells, but also via other regulation mechanisms. Finally, our data indicated that the combinatorial repertoire of the TcR-delta genes is limited, which has also been described for the TcR-gamma genes.

scholarly journals Enhancer-dependent and -independent steps in the rearrangement of a human T cell receptor delta transgene.

1994 ◽  
Vol 179 (1) ◽  
pp. 43-55 ◽  
Author(s):  
P Lauzurica ◽  
M S Krangel
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
T Cell Development ◽  
Cell Receptor ◽  
Cell Development ◽  
Gamma Delta ◽  
Delta Gene ◽  
Alpha Beta

The rearrangement and expression of T cell receptor (TCR) gene segments occurs in a highly ordered fashion during thymic ontogeny of T lymphocytes. To study the regulation of gene rearrangement within the TCR alpha/delta locus, we generated transgenic mice that carry a germline human TCR delta minilocus that includes V delta 1, V delta 2, D delta 3, J delta 1, J delta 3, and C delta segments, and either contains or lacks the TCR delta enhancer. We found that the enhancer-positive construct rearranges stepwise, first V to D, and then V-D to J. Construct V-D rearrangement mimics a unique property of the endogenous TCR delta locus. V-D-J rearrangement is T cell specific, but is equivalent in alpha/beta and gamma/delta T lymphocytes. Thus, either there is no commitment to the alpha/beta and gamma/delta T cell lineages before TCR delta gene rearrangement, or if precommitment occurs, it does not operate directly on TCR delta gene cis-acting regulatory elements to control TCR delta gene rearrangement. Enhancer-negative mice display normal V to D rearrangement, but not V-D to J rearrangement. Thus, the V-D to J step is controlled by the enhancer, but the V to D step is controlled by separate elements. The enhancer apparently controls access to J delta 1 but not D delta 3, suggesting that a boundary between two independently regulated domains of the minilocus lies between these elements. Within the endogenous TCR alpha/delta locus, this boundary may represent the 5' end of a chromatin regulatory domain that is opened by the TCR delta enhancer during T cell development. The position of this boundary may explain the unique propensity of the TCR delta locus to undergo early V to D rearrangement. Our results indicate that the TCR delta enhancer performs a crucial targeting function to regulate TCR delta gene rearrangement during T cell development.

scholarly journals Gamma/delta lineage relationship within a consecutive series of human precursor T-cell neoplasms

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2508-2518 ◽  
Author(s):  
JP de Villartay ◽  
AB Pullman ◽  
R Andrade ◽  
E Tschachler ◽  
O Colamenici ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Consecutive Series ◽  
Gene Rearrangements ◽  
Gamma Delta ◽  
Delta Gene ◽  
Gene Usage ◽  
Rearrangement Process ◽  
Gamma Delta T Cell

Abstract We analyzed the gene rearrangements associated with the newly described delta T-cell receptor (TCR) gene from a series of 19 consecutive precursor T-cell (lymphoblastic) neoplasms that represent discrete stages surrounding the TCR gene rearrangement process. Significantly, the delta TCR gene showed rearrangement in most (13 of 19) of these T cells, and in addition it was rearranged in two cells displaying no rearrangement for any other TCR gene. Our survey showed three types of delta gene rearrangements associated with cell-surface TCR expression that presumably represent usage of three V delta genes. This analysis demonstrates (1) a major subclass of human precursor T-cell neoplasms belonging to the gamma/delta T-cell receptor-rearranging subtype; (2) a narrow repertoire of human V delta gene usage; and (3) the utility of delta gene rearrangements as a diagnostic clonal marker in precursor T lymphoblastic neoplasms.

scholarly journals Surface expression of functional T cell receptor chains formed by interlocus recombination on human T lymphocytes.

1994 ◽  
Vol 180 (5) ◽  
pp. 1685-1691 ◽  
Author(s):  
F Davodeau ◽  
M A Peyrat ◽  
J Gaschet ◽  
M M Hallet ◽  
F Triebel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Structural Features ◽  
Gamma Delta ◽  
Cell Repertoire ◽  
Repertoire Selection ◽  
Alpha Beta

Structural diversity of lymphocyte antigen receptors (the immunoglobulin [Ig] of B cells and the alpha/beta or gamma/delta T cell receptor [TCR] of T cells) is generated through somatic rearrangements of V, D, and J gene segments. Classically, these recombination events involve gene segments from the same Ig or TCR locus. However, occurrence of "trans" rearrangements between distinct loci has also been described, although in no instances was the surface expression of the corresponding protein under normal physiological conditions demonstrated. Here we show that hybrid TCR genes generated by trans rearrangement between V gamma and (D) J beta elements are translated into functional antigen receptor chains, paired with TCR alpha chains. Like classical alpha/beta T cells, cells expressing these hybrid TCR chains express either CD4 or CD8 coreceptors and are frequently alloreactive. These results have several implications in terms of T cell repertoire selection and relationships between TCR structure and specificity. First, they suggest that TCR alloreactivity is determined by the repertoire selection processes operating during lymphocyte development rather than by structural features specific to V alpha V beta regions. Second, they suggest the existence of close structural relationships between gamma/delta and alpha/beta TCR and more particularly, between V gamma and V beta regions. Finally, since a significant fraction of PBL (at least 1/10(4)) expressed hybrid TCR chains on their surface, these observations indicate that trans rearrangements significantly contribute to the combinatorial diversification of the peripheral immune repertoire.

scholarly journals Rearrangement of the T-cell receptor delta genes in human T-cell leukemias

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 559-565 ◽  
Author(s):  
L Foroni ◽  
M Laffan ◽  
T Boehm ◽  
TH Rabbitts ◽  
D Catovsky ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Gamma Delta ◽  
Human T Cell ◽  
Delta Gene ◽  
Alpha Beta

Abstract Two distinct types of T-cell receptors (TCR), designated alpha beta and gamma delta, have been identified on the surface of T cells. In the adult, T cells bearing the gamma delta TCR are a minority and they have the phenotype CD3+, CD4-, CD8-/+. By using appropriate probes, rearrangements of the TCR alpha, beta, and gamma genes have been extensively investigated in a variety of lymphoproliferative disorders. Because the TCR delta gene has been cloned only recently, no comparable information exists with respect to this in human leukemias. We report the analysis of the TCR delta gene configuration in 21 T-cell acute and chronic leukemias, 40 B-cell leukemias, 4 acute myeloid leukemias of difficult classification, and 12 normal controls. The TCR delta genes were structurally modified in all T-cell disorders and in germ-line configuration in all controls and all but one case of non-T-cell leukemias tested. In one case of T-chronic lymphocytic leukemia (CD3+, CD4-, CD8+) we found rearrangement and expression of TCR gamma and delta (but not alpha and beta), suggesting that leukemic transformation took place in a cell bearing a TCR gamma delta rather than a TCR alpha beta. In two cases of pre-T-acute lymphoblastic leukemia, only delta was rearranged out of the three TCR genes tested. This finding is in keeping with the suggestion that the TCR delta gene might be the first to rearrange in T cell ontogeny, and that its mode of rearrangement may play a role in the subsequent choice of the cell between production of a TCR alpha beta or gamma delta. Thus, TCR delta chain gene analysis can provide novel information of the clonal nature of T-cell disorders, particularly if the analysis of the beta and gamma genes has not been helpful.

scholarly journals Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression.

1990 ◽  
Vol 4 (8) ◽  
pp. 1304-1315 ◽  
Author(s):  
S R Carding ◽  
S Kyes ◽  
E J Jenkinson ◽  
R Kingston ◽  
K Bottomly ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Developmentally Regulated ◽  
Delta Gene

scholarly journals Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor alpha/beta lineage: T cell receptor delta gene deletion mechanism affects multiple genes.

1993 ◽  
Vol 177 (4) ◽  
pp. 965-977 ◽  
Author(s):  
T M Breit ◽  
E J Mol ◽  
I L Wolvers-Tettero ◽  
W D Ludwig ◽  
E R van Wering ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Complex Analysis ◽  
Gene Promoter ◽  
Cell Receptor ◽  
Careful Examination ◽  
Gene Deletions ◽  
Site Specific ◽  
Delta Gene ◽  
Alpha Beta

Site-specific deletions in the tal-1 gene are reported to occur in 12-26% of T cell acute lymphoblastic leukemias (T-ALL). So far two main types of tal-1 deletions have been described. Upon analysis of 134 T-ALL we have found two new types of tal-1 deletions. These four types of deletions juxtapose the 5' part of the tal-1 gene to the sil gene promoter, thereby deleting all coding sil exons but leaving the coding tal-1 exons undamaged. The recombination signal sequences (RSS) and fusion regions of the tal-1 deletion breakpoints strongly resemble the RSS and junctional regions of immunoglobulin/T cell receptor (TCR) gene rearrangements, which implies that they are probably caused by the same V(D)J recombinase complex. Analysis of the 134 T-ALL suggested that the occurrence of tal-1 deletions is associated with the CD3 phenotype, because no tal-1 deletions were found in 25 TCR-gamma/delta + T-ALL, whereas 8 of the 69 CD3- T-ALL and 11 of the 40 TCR-alpha/beta + T-ALL contained such a deletion. Careful examination of all TCR genes revealed that tal-1 deletions exclusively occurred in CD3- or CD3+ T-ALL of the alpha/beta lineage with a frequency of 18% in T-ALL with one deleted TCR-delta allele, and a frequency of 34% in T-ALL with TCR-delta gene deletions on both alleles. Therefore, we conclude that alpha/beta lineage commitment of the T-ALL and especially the extent of TCR-delta gene deletions determines the chance of a tal-1 deletion. This suggests that tal-1 deletions are mediated via the same deletion mechanism as TCR-delta gene deletions.

Sign in / Sign up

Export Citation Format

Share Document