Rearrangement of two distinct T-cell γ-chain variable-region genes in human DNA

Selective cloning procedures for T-cell-specific complementary DNAs have revealed the existence of a gene designated1 γ as well as the main antigen receptor α- and β-chain genes2–10. The γ-chain genes undergo rearrangement during T-cell differentiation but the patterns and complexity of such rearrangements differ markedly in mouse11–13 and human14. In mouse, a panel of cytotoxic T-lymphocyte clones exhibit the same rearrangement pattern with a γ-chain gene probe11 and a set of three γ-chain variable (V) genes have been identified in the DNA12. Clonal diversity in mouse seems to be confined to V–J (joining) regions11. In contrast, human T-cell lines exhibit diverse rearrangements14 suggestive of a family of differing Vγ genes variously rearranging to the two γ-chain constant (C) region genes14,15. Here we report the cloning of two very different Vγ genes rearranged to J segments upstream of the two human Cγ genes. Both Vγ genes are rearranged productively but nucleotide sequence comparison shows that they possess very little homology with each other. This shows that human T-cell Vγ genes exist which differ significantly from each other at the nucleotide level and that such diverse genes can be usefully rearranged in different T cells.

[1]  T. Waldmann,et al.  Human γ-chain genes are rearranged in leukaemic T cells and map to the short arm of chromosome 7 , 1985, Nature.

[2]  R. Staden.  A new computer method for the storage and manipulation of DNA gel reading data. , 1980, Nucleic acids research.

[3]  K. Chen,et al.  Fusion of an immunoglobulin variable gene and a T cell receptor constant gene in the chromosome 14 inversion associated with T cell tumors , 1985, Cell.

[4]  S. Tonegawa,et al.  Structure, organization, and somatic rearrangement of T cell gamma genes , 1985, Cell.

[5]  J. Vieira,et al.  The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. , 1982, Gene.

[6]  S. Tonegawa,et al.  Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences , 1984, Nature.

[7]  M. Minden,et al.  Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[8]  P. Leder,et al.  Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in burkitt lymphoma , 1984, Cell.

[9]  M. Lefranc,et al.  Two tandemly organized human genes encoding the T-cell γ constant-region sequences show multiple rearrangement in different T-cell types , 1985, Nature.

[10]  T. Rabbitts,et al.  Complexity of human T-cell antigen receptor β-chain constant- and variable-region genes , 1984, Nature.

[11]  Rodger Staden,et al.  Graphic methods to determine the function of nucleic acid sequences , 1984, Nucleic Acids Res..

[12]  R. Warnke,et al.  Monoclonal antibody and enzymatic profiles of human malignant T-lymphoid cells and derived cell lines. , 1984, Cancer research.

[13]  S. Tonegawa,et al.  Expression of the T-cell-specific γ gene is unnecessary in T cells recognizing class II MHC determinants , 1985, Nature.

[14]  L. Hood,et al.  The human t cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene , 1984, Cell.

[15]  F. Sanger,et al.  Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. , 1980, Journal of molecular biology.

[16]  S. Tonegawa,et al.  Limited diversity of the rearranged T-cell γ gene , 1985, Nature.

[17]  Mark M. Davis,et al.  Sequence relationships between putative T-cell receptor polypeptides and immunoglobulins , 1984, Nature.

[18]  S. Tonegawa,et al.  A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes , 1984, Nature.

[19]  Tak W. Mak,et al.  A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains , 1984, Nature.

[20]  Mark M. Davis,et al.  Genomic organization and sequence of T-cell receptor β-chain constant- and joining-region genes , 1984, Nature.

[21]  Mark M. Davis,et al.  A third type of murine T-cell receptor gene , 1984, Nature.

[22]  J. Yagüe,et al.  Primary structure of human T-cell receptor α-chain , 1984, Nature.

[23]  S. Brenner,et al.  A new selective phage cloning vector, λ2001, with sites for XbaI, BamHI, HindIII, EcoRI, SstI and XhoI , 1984 .