Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex

Furley, Andrew J.; Mizutani, Shuki; Weilbaecher, Katherine N.; Dhaliwal, H. S.; Ford, AM; Li, Chan; Molgaard, H. V.; Toyonaga, Barry; Mak, Tak W.; Elsen, Peter van den; Gold, Daniel P.; Terhorst, Cox; Greaves, MF

doi:10.1016/0092-8674(86)90861-5

Cited by 203 publications

(60 citation statements)

References 73 publications

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“…Another phenomenon that might cause interpretation problems, is the partial resistance to digestion of the EcoRI site between the J␤2 and the C␤2 region. 6,21 Incomplete digestion of this EcoRI site leads to an additional germline band of 8.0 kb (of variable density, depending on the degree of incompleteness of digestion) next to the common 4.2 kb germline band upon hybridization of EcoRI digests with the TCRBJ2 probe ( Table 2 and Figures 1 and 4). Nevertheless, in particular cases a true rearrangement might result in a band of similar size ( Figure 4); discrimination between underdigestion and true rearrangement in such cases is possible by sequential hybridization of EcoRI digests with the TCRBJ2 and TCRBC probes (Figure 4).…”

Section: Analysis Of Polymorphismsmentioning

confidence: 99%

“…In a similar way, the resistance to digestion also applies to the HindIII site between C␤2 exon 1 and exon 2, but partial digestion at this position is less frequently observed and thus rarely causes misinterpretation. 6,21 Sensitivity of detection of clonal T cell populations with TCRB genomic DNA probes Sensitivity of detection of TCRB gene rearrangements was evaluated in serial dilutions of T-ALL DNA (with multiple ␤1 and ␤2 rearrangements) into normal PB MNC DNA. Upon hybridization with the TCRBJ2 probe two rearranged bands were observed in the undiluted sample.…”

Section: Analysis Of Polymorphismsmentioning

confidence: 99%

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Detection of T cell receptor beta (TCRB) gene rearrangement patterns in T cell malignancies by Southern blot analysis

1999

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Reliable detection of clonal T cell receptor beta (TCRB) gene rearrangements is essential for clonality assessment of suspect T cell proliferations. Since no appropriate Southern blot probes were available, we developed a new set of optimized TCRB gene probes. The TCRBJ1 and TCRBJ2 probes are positioned just downstream of the J␤1 and J␤2 gene segments, respectively, and can be used for detection of both incomplete D␤-J␤ and complete V␤-J␤ rearrangements, whereas the TCRBD1U and TCRBD2U probes upstream of the D␤ segments can be used to confirm incomplete D␤-J␤ rearrangements. Less frequently occurring V␤-D␤ rearrangements can easily be detected via the downstream TCRBD1 and TCRBD2 probes. Although both EcoRI and HindIII are appropriate restriction enzymes to be used in combination with all these probes, falsepositivity due to partial digestion of the EcoRI site in the J␤2-C␤ intron has to be excluded via the TCRBC probe. Application of the TCRB probes in a large series of nearly 200 T cell malignancies revealed clonal rearrangements in all immature and mature TCR␣␤ + T cell malignancies, in the vast majority of TCR␥␦ + T cell acute lymphoblastic leukemias (T-ALL) (approximately 95%) and even in most CD3 − T-ALL (approximately 80%). TCRB gene rearrangement patterns differed between the various categories of T cell malignancies. An increased frequency of complete V␤-J␤1 rearrangements was observed in TCR␣␤ + T-ALL as compared to CD3 − and TCR␥␦ + T-ALL (33% vs 16% and 11%, respectively), and also incompletely rearranged V-D, D-D, or D-J alleles in the ␤2 region occurred more frequently in TCR␣␤ + cases than in CD3 − and TCR␥␦ + T-ALL (27% vs 15% and 18%, respectively). Furthermore, in comparison to TCR␣␤ + T-ALL, less V␤-J␤1 and more V␤-J␤2 rearrangements were detected in mature TCR␣␤ + T cell malignancies. The occurrence of the different types of TCRB rearrangement patterns has implications for PCR-based clonality assessment and for PCR-based detection of minimal residual disease via TCRB gene analysis. For instance, focussing on the ␤2 region of T-ALL will allow detection of rearrangements in 70%, 75%, and 90% of CD3 − , TCR␥␦ + , and TCR␣␤ + cases, respectively. Therefore the here-described results will facilitate the design of the most appropriate primer sets for PCR analysis of TCRB gene rearrangements at the DNA level.

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Section: Analysis Of Polymorphismsmentioning

confidence: 99%

Section: Analysis Of Polymorphismsmentioning

confidence: 99%

Detection of T cell receptor beta (TCRB) gene rearrangement patterns in T cell malignancies by Southern blot analysis

1999

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“…Mutation analysis of 5qNCA by genomic sequencing of AML and MDS samples 5qNCA was investigated for mutations by sequencing the complete coding region of all 24 exons in genomic DNA; three AML cell lines with chromosome 5 deletion, KG-1, HL-60, and MUTZ-1, (Furley et al, 1986;Gallagher et al, 1979;Steube et al, 1997) along with 11 clinical leukemia samples with 5q abnormalities, were studied. Primer design was based on intronic sequences and mutations were detected by comparing the resulting sequence to the wild-type 5qNCA sequence.…”

Section: Growth Suppressive Properties Of 5qncamentioning

confidence: 99%

A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31

Gomes

Horrigan

et al. 2001

Oncogene

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Interstitial deletion or loss of chromosome 5, del(5q) or 75, is a frequent ®nding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identi®ed a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc ®nger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted. Oncogene (2001) 20, 6946 ± 6954.

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“…Subsequently, a chains are expressed. This allows the formation of the Ti-al3 heterodimer which, in turn, allows the full TCR to appear on the cell surface (Furley et al, 1986;Van Dongen et al, 1987). All of these observations suggest that delivery of TCR complexes to the cell surface requires the synthesis of all of the receptor chains.…”

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confidence: 99%

“…Transfecting the genes for Ti-ct or Ti-13 into mutant cells deficient in the synthesis of these chains can restore surface expression of functional TCRs in these cells (Ohashi et al, 1985;Saito et al, 1987b). T cell precursors isolated from fetal thymus or leukemic cells corresponding to the earliest stages of intrathymic T cell maturation transcribe mRNAs for the 13 and CD3 chains but not for the a chain (Furley et al, 1986;Van Dongen et al, 1987;Samelson et al, 1985b;Raulet et al, 1985;Snodgrass et al, 1985). TCR chains other than the a chain are synthesized in these cells but fail to be transported to the plasma membrane (Hannum et al, 1987;Furley et al, 1986;Farr et al, 1985).…”

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confidence: 99%

Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

Chen

Bonifacino

Yuan

et al. 1988

The Journal of Cell Biology

139

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Abstract. We have examined the fate of newly synthesized T cell antigen receptor (TCR) subunits in a T cell hybridoma deficient in expression of the clonotypic 13 chain. Synthesis and assembly of the remaining chains proceed normally but surface expression of TCR chains is undetectable in these cells. A variety of biochemical and morphological techniques has been used to show that the TCR chains in these cells fail to be transported to any of the Golgi cisternae. Instead, they are retained in a pre-Golgi compartment which is either part of or closely related to the endoplasmic reticulum. The CD3-6 chain is degraded by a nonlysosomal process that is inhibited at temperatures at or below 27°C. By contrast, the remaining chains (CD3-e, CD3-'t, and ~) are very stable over 7 h. We propose possible mechanisms that may explain the differential fate of TCR chains retained in a pre-Golgi compartment.

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Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex

Cited by 203 publications

References 73 publications

Detection of T cell receptor beta (TCRB) gene rearrangement patterns in T cell malignancies by Southern blot analysis

Detection of T cell receptor beta (TCRB) gene rearrangement patterns in T cell malignancies by Southern blot analysis

A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31

Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

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