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Gene placement and competition control T cell receptor gamma variable region gene rearrangement.

ABSTRACT: The production of distinct sets of T cell receptor (TCR) gammadelta(+) T cells occurs in an ordered fashion in thymic development. The Vgamma3 and Vgamma4 genes, located downstream in the TCRgamma Cgamma1 gene cluster, are expressed by the earliest waves of developing TCRgammadelta(+) T cells in the fetal thymus, destined for intraepithelial locations. Upstream Vgamma2 and Vgamma5 genes are expressed in later waves in the adult and constitute most TCRgammadelta(+) T cells in secondary lymphoid tissue. This developmental pattern is caused in part by a preference for rearrangements of the downstream Vgamma3 and Vgamma4 genes in the early fetal stage, which switches to a preference for rearrangements of the upstream Vgamma2 and Vgamma5 gene rearrangements in the adult. Our gene targeting studies show that the downstream Vgamma genes rearrange preferentially in the early fetal thymus because of their downstream location, independent of promoter or recombination signal sequences and unrelated to the extent of germline transcription. Remarkably, gene deletion studies show that the downstream Vgamma genes competitively inhibit upstream Vgamma rearrangements at the fetal stage. These data provide a mechanism for specialization of the fetal thymus for the production of T cells expressing specific Vgamma genes.

SUBMITTER: Xiong N

PROVIDER: S-EPMC2292229 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Gene placement and competition control T cell receptor gamma variable region gene rearrangement.

Xiong Na N Zhang Li L Kang Chulho C Raulet David H DH

The Journal of experimental medicine 20080331 4

The production of distinct sets of T cell receptor (TCR) gammadelta(+) T cells occurs in an ordered fashion in thymic development. The Vgamma3 and Vgamma4 genes, located downstream in the TCRgamma Cgamma1 gene cluster, are expressed by the earliest waves of developing TCRgammadelta(+) T cells in the fetal thymus, destined for intraepithelial locations. Upstream Vgamma2 and Vgamma5 genes are expressed in later waves in the adult and constitute most TCRgammadelta(+) T cells in secondary lymphoid t ...[more]

PMID: 18378791

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Project description:AimTo analyze the characterization of T-cell receptor-gamma (TCR-gamma) gene rearrangement in the gastrointestinal lymphomas and evaluate the value of PCR-SSCP analysis in gastrointestinal lymphomas investigation.MethodsTCR-gamma gene rearrangement segments of gastrointestinal lymphomas were cloned and sequenced. Single clone plasmid and mixed clone plasmids were subsequently submitted to PCR-SSCP analysis to investigate the relationship between the number of amplified clones and band patterns of the amplified products. The PCR products of TCR-gamma gene rearrangement of 40 gastrointestinal lymphomas were electrophoresed on agarose gels and the positive cases on agarose gels were studied by SSCP analysis.ResultsThe sequencing showed that TCR-gamma gene rearrangement of the gastrointestinal lymphomas included functional gene and pseudogene with extensive variety in the junctional regions. In SSCP analysis, the number of the single-stranded bands was about two times of the number of amplified clones, and double-stranded band became broad with the increased number of the amplified clones. Thirteen of the 25 B-cell gastrointestinal lymphomas and 14 of the 15 gastrointestinal T-cell lymphomas were positive detected on agarose gel electrophoresis. Of the positive cases detected by SSCP analysis, 3 B-cell lymphomas and 13 T-cell lymphomas showed positive bands. The other cases showed only smears. The rearranged pattern included 13 monoallelic gene rearrangements and 3 biallelic or oligoclonal gene rearrangements.ConclusionThe pattern of TCR-gamma gene rearrangement in gastrointestinal lymphomas are similar to that of the nodular lymphomas. PCR-SSCP analysis for TCR-gamma gene rearrangement can be applied both for adjuvant diagnosis of gastrointestinal lymphomas and analysis of the gene rearrangement pattern. The ratio of TCR-gamma gene rearrangements occurred in T-cell gastrointestinal lymphomas is significantly higher than that in B-cell gastrointestinal lymphomas. The gene rearrangement pattern involves monoallelic and biallelic (or oligoclonal) gene rearrangement.

Dataset Information

Gene placement and competition control T cell receptor gamma variable region gene rearrangement.

Publications

Gene placement and competition control T cell receptor gamma variable region gene rearrangement.

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