Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements.

Saito, Haruo; Koyama, Takuma; Georgopoulos, Katia; Haser, Wayne G.; LeBien, Tucker W.; Tonegawa, Susumu; Terhorst, Cox

doi:10.1073/pnas.84.24.9131

Cited by 47 publications

(27 citation statements)

References 28 publications

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“…The CD3␥ gene, consisting of seven exons, is highly homologous to the CD3␦ gene (25), and their transcription seems to be controlled by common regulatory elements (26). However, it has been suggested that ␥ and ␦ have a distinct function.…”

Section: Discussionmentioning

confidence: 99%

Molecular Cloning of pTAC12 an Alternative Splicing Product of the CD3γ Chain as a Component of the Pre-T Cell Antigen-Receptor Complex

Takase¹,

Okazaki²,

Wakizaka³

et al. 1998

Journal of Biological Chemistry

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We have reported that a 12-kDa molecule (pTAC12 as a pre-T cell receptor (TCR)-associated chain) was associated as a dimer with the pre-TCR complex as well as the clonotype-independent CD3 complex on the cell surface of immature thymocytes. We now report by protein sequencing and molecular cloning that pTAC12 is an alternatively spliced product of the CD3␥ chain lacking exon 4 containing the transmembrane region. The transcript of pTAC12 is expressed in most T cell lineages and parallels the expression of CD3␥. However, the pTAC12 protein is expressed on the cell surface of immature thymocytes but not mature T cells, despite the fact that mature T cells express a low level of pTAC12 in association with the TCR complex within the cells. These results indicate that pTAC12 may play a special role for the transport/expression and assembly of the pre-TCR⅐CD3 complex as well as the clonotype-independent CD3 complex in immature thymocytes.Thymocyte differentiation generates a functional repertoire of T cells competent for carrying out the immune response. The mechanism of thymocyte selection through the T cell receptor (TCR) 1 has been extensively analyzed, whereas the regulation of the development prior to the expression of the TCR␣␤ dimer is still largely unknown. Surface expression of the TCR␤ chain regulates a crucial step of early T cell development from CD4 Ϫ CD8 Ϫ (double negative) to CD4 ϩ CD8 ϩ (double positive) stages in TCR␣␤-expressing T cells (1). It was demonstrated that these immature thymocytes express the pre-TCR complex, which is composed of the pre-TCR␣ chain (pT␣) and the TCR␤ chain in association with the CD3 complex, before the TCR␣ gene is rearranged and expressed (2, 3). Analyses of TCR␤-(4) and pT␣-deficient mice (5) have revealed a critical role of the pre-TCR complex in the regulation of early thymocyte development. The structure of pre-TCR resembles that of pre-B cell antigen receptor, which is composed of the -heavy chain, 5, and VpreB. Although pT␣ may be equivalent to 5 because of the fact that both consist of an Ig-like constant domain, a "VpreT" molecule equivalent to VpreB has not been identified yet. Because it has been shown that CD3 and ZAP-70 are phosphorylated after stimulation by cross-linking of the pre-TCR complex with anti-CD3⑀ mAb in a cell line (6) and that Lck plays an important role for thymic development (7-9), signaling through the pre-TCR complex might be similar to that in mature T cells. However, because the physical association between the pre-TCR complex and CD3 is very weak (10 -13) and thymocytes differentiate to the double positive stage in CD3-deficient mice (14 -17), CD3 may not be essential for early T cell development. Differential assembly of the components within the pre-TCR complex may suggest a unique regulation of its assembly and expression.In addition to the pre-TCR⅐CD3 complex, the clonotype-independent CD3 (CIC) complex lacking TCR␣ and -␤ chains is present on the cell surface of immature thymocytes (18). The CIC complex, which might also be associat...

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Section: Discussionmentioning

confidence: 99%

Molecular Cloning of pTAC12 an Alternative Splicing Product of the CD3γ Chain as a Component of the Pre-T Cell Antigen-Receptor Complex

Takase¹,

Okazaki²,

Wakizaka³

et al. 1998

Journal of Biological Chemistry

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“…As a rule, members of the immunoglobulin supergene family encode their signal sequences by using a single exon (26). The first exceptions to this rule were the mouse and human CD3 y chains, which utilize one exon to encode the hydrophobic region of the leader peptide and another to encode the signal peptidase cleavage site (30,31). The FcRI a-chain gene (28) and the FcYRIIa and FcRIIb genes now represent additional exceptions in the immunoglobulin gene superfamily to the "signal peptide-single exon" rule.…”

Section: Discussionmentioning

confidence: 99%

Genomic organization of mouse Fc gamma receptor genes.

Kulczycki

Webber

Soares

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…The structure of these different promoter regions may be used by activation mechanisms specific of genes expressed during early T-cell differentiation, like the CD3 6 gene and the TRGV9 and TRDV2 genes. Note that other genes which are also expressed early in T-cell differentation, the CD3 y [51] and E [52] genes, the CD2 gene [53] and the mouse Thy-l [54] lack TATA, CAAT and GC boxes. Finally, the presence of a characteristic decanucleotide in the promoter regions of the TRDV2 and TRGV9 genes may have some biological significance, since both TRDV2 and TRGV9 genes both appear to be expressed early in T-cell differentiation [31, 321. …”

Section: Discussionmentioning

confidence: 99%

The promoter regions of the T‐cell receptor V9 γ (TRGV9) and V2 δ (TRDV2) genes display short direct repeats but no TATA box

Dariavach

Lefranc

1989

FEBS Letters

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T lymphocytes expressing the T-cell yS receptor have been shown to express preferentially the T-cell receptor V9 y(TRGV9) gene, in association with the T-cell receptor V2 S(TRDV2) gene. In this paper, we report that the promoter regions of the TRDM and TRGV9 genes, which are preferentially expressed early in T-cell differentiation, display short direct repeats but no TATA box, in contrast to the Vy genes belonging to subgroup I. The TCCTCAGT octanucleotide found 100 pb upstream of the ATG of the HD-Mar Va transcript, a TcR Va gene without a TATA box, is observed upstream of TRDV2 but not TRGV9. Of interest is the presence of a characteristic decanucleotide AGGTGGT(T)GAG in the promoter regions of both the TRDV2 and TRGV9 genes.

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Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements.

Cited by 47 publications

References 28 publications

Molecular Cloning of pTAC12 an Alternative Splicing Product of the CD3γ Chain as a Component of the Pre-T Cell Antigen-Receptor Complex

Molecular Cloning of pTAC12 an Alternative Splicing Product of the CD3γ Chain as a Component of the Pre-T Cell Antigen-Receptor Complex

Genomic organization of mouse Fc gamma receptor genes.

The promoter regions of the T‐cell receptor V9 γ (TRGV9) and V2 δ (TRDV2) genes display short direct repeats but no TATA box

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