Sizing of the human T cell receptor alpha locus and detection of a large deletion in the Molt-4 cell line.

The human T cell receptor alpha (TCR-alpha) chain gene consists of discontinuous DNA segments encoding multiple variable (V), multiple joining (J), and one constant (C) region. Unlike other immunoglobulin or TCR genes, however, the TCR-alpha locus exhibits an unusual dispersal of J segments that occupy a region of greater than 50 kilobases (kb) upstream of the C region, with the exact size still unknown. We report here the study of the TCR-alpha genetic locus by using pulsed-field gel electrophoresis (PFGE), which permits the separation of large DNA fragments. Analysis of DNA prepared from normal peripheral blood mononuclear cells, human endothelial cells, and a B cell line demonstrates that both V and C sequences are contained within a single 400-kb SfiI restriction fragment. PFGE analysis of the T cell line Molt 4 suggests a greater than 600-kb deletion involving the TCR-alpha gene.

[1]  Mark M. Davis,et al.  A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation , 1987, Nature.

[2]  L. Hood,et al.  Genomic organization of the mouse T-cell receptor beta-chain gene family. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  F. Collins,et al.  Construction of a general human chromosome jumping library, with application to cystic fibrosis. , 1987, Science.

[4]  F. Alt,et al.  A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes , 1986, Nature.

[5]  T. Mak,et al.  Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Minden,et al.  Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor α-chain , 1985, Nature.

[7]  E. Reinherz,et al.  Genes encoding the T-cell receptor alpha and beta subunits are transcribed in an ordered manner during intrathymic ontogeny. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[8]  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.

[9]  A. Houghton,et al.  Loss of polymorphic restriction fragments in malignant melanoma: implications for tumor heterogeneity. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  L. Hood,et al.  T cell antigen receptors and the immunoglobulin supergene family , 1985, Cell.

[11]  D. Schwartz,et al.  Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis , 1984, Cell.

[12]  A. Feinberg,et al.  A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. , 1983, Analytical biochemistry.

[13]  W. Chan,et al.  Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia. , 1987, Blood.

[14]  C R Cantor,et al.  Strategies for mapping and cloning macroregions of mammalian genomes. , 1987, Methods in enzymology.