Predominant variable region gene usage by gamma/delta T cell receptor-bearing cells in the adult thymus.

Korman, Alan J.; Marusić-Galesić, S; Spencer, David M.; Kruisbeek, Ada M.; Raulet, David H.

doi:10.1084/jem.168.3.1021

Cited by 59 publications

(33 citation statements)

References 44 publications

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“…These data suggest a limited genomic repertoire of the TCR 6 gene, as previously proposed for the murine TCR 6 gene (4,10,67,69). Analysis of functional TCR y genes reveals that the functional diversity may be limited to only three variable regions (Vy5, Vy8, and Vy9) (14, 30, 68).…”

Section: Resultsmentioning

confidence: 61%

“…Analysis of functional TCR y genes reveals that the functional diversity may be limited to only three variable regions (Vy5, Vy8, and Vy9) (14, 30, 68). In TCR 6 limited usage of VA regions has been demonstrated in mouse thymocytes and T-lymphocytes and in a number of T y/6 cell lines (3,4,5,7,10,(66)(67)(68)(69). We therefore sought to determine whether additional functional TCR 6 rearrangements exist in humans.…”

Section: Resultsmentioning

confidence: 99%

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T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

Griesinger

Greenberg²,

Kersey³

1989

J. Clin. Invest.

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We have studied recombinatorial events of the T cell receptor a and y chain genes in hematopoietic malignancies and related these to normal stages of lymphoid differentiation. T cell receptor a gene recombinatorial events were found in 91% of acute T cell lymphoblastic leukemia, 68% of non-T, non-B lymphoid precursor acute lymphoblastic leukemia (ALL) and 80% of mixed lineage acute leukemias. Mature B-lineage leukemias and acute nonlymphocytic leukemias retained the Tcell receptor a gene in the germline configuration. The incidence of T cell receptor 'y and was particularly high in CD10CD19+ non-T, non-B lymphoid precursor ALL. In lymphoid precursor ALL, T cell receptor a was frequently rearranged while T cell receptor y was in the germline configuration. This suggests that TCR a rearrangements may precede TCR y rearrangements in lymphoid ontogeny. In T-ALL, only concordant T cell receptor a and y rearrangements were observed. Several distinct rearrangements were defined using a panel of restriction enzymes. Most of the rearrangements observed in T-ALL represented joining events of Jb1 to upstream regions. In contrast, the majority of rearrangements in lymphoid precursor ALL most likely represented D-D or V-D rearrangements, which have been found to be early recombinatorial events of the TCR a locus. We next analyzed TCR a rearrangements in five CD3'TCR'y/5' ALL and cell lines. One T-ALL, which demonstrated a different staining pattern with monoclonal antibodies against the products of the TCR -y/S genes than the PEER cell line, rearranges Jb1 to a currently unidentified variable region.

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Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 99%

T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

Griesinger

Greenberg²,

Kersey³

1989

J. Clin. Invest.

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“…Thus, the exclusively used DV4S8A2 gene segment differs from DV4S8 by only five amino acid residues (3). This limited extent of variation may be ac-counted for by allelic polymorphism between the BALB/c mouse strain used in this analysis and the C57BL/6 strain from which the CD4 Ϫ CD8 Ϫ ␥␦ thymocyte hybridoma expressing DV4S8 was derived (33). Similarly, DV10S7A2 from BALB/c neonates in this study differs by four amino acid replacements from DV10S7 (3), previously isolated from a CD4 Ϫ CD8 Ϫ ␥␦ thymocyte hybridoma from C57BL/6 mice.…”

Section: Second Wave: Preferential Usage Of the Proximal Cluster Of Dmentioning

confidence: 87%

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

Weber-Arden

Wilbert

Kabelitz

et al. 2000

The Journal of Immunology

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Taking advantage of a PCR technique that allows amplification of all variable region genes with equal efficiency, we defined three novel waves of TCR δ-chain transcription during thymic ontogeny. The canonical DV101-D2-J2 rearrangement was confined to a narrow window from days 14 to 18 of gestation, indicating that the postulated two consecutive γδ precursor waves bearing this canonical DV101 rearrangement will coincide on day 16. Neonatal δ-chain transcripts used a second wave of diverse Vα gene segments that are exclusively located in the δ locus-proximal gene cluster of intermingled single members of different Vα subfamilies. In the adult, only expression of a clan of three homologous subfamilies, ADV7, DV104, and ADV17, persists. The members of the ADV7 subfamily are also scattered across the α locus, but their usage does not show the position-dependent bias of the other Vα-to-δ rearrangements.

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“…Our interpretation of the observations mentioned above is that TCR 8 is the first TCR locus to undergo recombination and that the effect of scid on T-cell lineage development is first manifest during or shortly after the initiation of D~I-, D~2-, and J~l-associated rearrangements. Ordered rearrangement within and between different TCR loci is well documented; for example, TCR 8 and ~/loci show ordered rearrangement of V gene elements (Garman et al 1986;Heilig and Tonegawa 1986;Chien et al 1987b;Elliott et al 1988;Iwashima et al 1988;Korman et al 1988Korman et al , 1989Tokagaki et al 1989), TCR ~/and ~ genes rearrange before TCR ~ genes (Haars et al 1988), and TCR 8 gene rearrangement has been shown to occur at least as early as that of TCR ~ and genes (Chien et al 1987b).…”

Section: Genes and Development 1361mentioning

confidence: 99%

T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor delta gene recombination.

Carroll

Bosma²

1991

Genes Dev.

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Scid mice lack functional lymphocytes because they carry a mutation that impairs rearrangement of immunoglobulin and T-cell receptor (TCR) genes. Rearrangement of TCR ~, but not ~, and 13 genes, was routinely observed in DNA of scid thymocytes and thymocyte hybridomas. TCR 8 gene rearrangements appeared to involve DS1, D82, and JSl elements only; rearrangement of elements upstream of D~I (e.g., VS1) was not observed, and transcripts corresponding to fully assembled TCR 8 genes (VDJ8 or VDDJS) were not detected in RNA from scid thymocytes. These findings suggest that DS1, D82, and JS1 may be among the first TCR gene elements to undergo recombination and that scid T-lineage cells are developmentally arrested during or shortly after this stage of differentiation. One class of TCR 8 recombination fragments (D82-JS1) was amplified by the polymerase chain reaction (PCR) and cloned, and the recombination junctions were sequenced. Most fragments showed normal coding joints. Interestingly, five of seven coding joints that lacked N insertions showed evidence of recombination between short stretches (2-3 bp) of homologous sequence. As discussed, the general absence of VS-, J~/-, and ll3-associated rearrangements, despite the occurrence of normal D82-JS1 rearrangements, raises the possibility that the scid mutation may cause premature cessation of TCR gene recombination and thereby arrest early T-cell development.[Key Words: scid mice; T-cell receptor; T-cell development; polymerase chain reaction] Received January 14, 1991; revised version accepted May 17, 1991.Mice homozygous for the autosomal recessive mutation, scid (scid mice) are severely deficient in mature lymphocytes (Bosma et al. 1983). Early B-and T-lineage-committed cells are clearly present in scid lymphopoietic tissues but are unable to differentiate into functional B and T lymphocytes. This developmental arrest is believed to reflect a defect in the system responsible for the recombination of V (variable), D (diversity), and J (joining) gene elements that code for immunoglobulin and T-cell receptor (TCR) variable regions. Evidence of this defect is seen in rearranged immunoglobulin heavy-chain (IgH) genes of transformed scid pre-B cell lines (Schuler et al. 1986;Hendrickson et al. 1988;Kim et al. 1988;Malynn et al. 1988;Okazaki et al. 1988;Blackwell et al. 1989) and rearranged TCR ~/and genes of scid thymic lymphomas (Schuler et al. 1986(Schuler et al. , 1990. Most such rearranged genes show abnormal deletions of D-and J-or V-and J-coding elements, frequently extending 1 kb or more. In addition, transfection of transformed scid lymphocytes with extrachromosomal (Lieber et al. 1988) or retroviral recombination substrates (Ferrier et al. 1990;Hendrickson et al. 1990) has revealed a defect in the recombinase activity associated with VDJ 1Present address: Albany Medical College, Department of Microbiology and Immunology, Albany, New York 12208 USA. recombination: Although this activity can recognize, cleave, and join the recombination signal sequences that flank...

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Predominant variable region gene usage by gamma/delta T cell receptor-bearing cells in the adult thymus.

Cited by 59 publications

References 44 publications

T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor delta gene recombination.

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