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B Toyonaga

Publications and source records attributed to B Toyonaga.

18 recordsLinked to original sources
PubMed1987

Repertoire of the human T cell gamma genes: high frequency of nonfunctional transcripts in thymus and mature T cells.

To further understand the structural diversity and function of the human T cell-specific gamma gene, 20 human gamma gene cDNA from both thymocyte and peripheral blood T lymphocyte libraries were sequenced and analyzed. Evidence of greater germ-line multiplicity and more extensive use of junctional flexibility, N-region diversity and perhaps D gamma gene segment incorporation was observed. In spite of the larger gamma gene repertoire found in humans compared to mice, the potential of the human gamma gene message to encode a functional product appears to be severely limited. In addition to the extremely low levels of gamma gene expression observed, each of the 20 gamma gene cDNA exhibit some form of deleterious mutation defect. This is in sharp contrast to the finding that human and mouse T cell antigen receptor alpha and beta messages isolated from various sources have functional coding potential in most cases. Thus, the role of the human T cell gamma gene becomes even more uncertain than before.

Amino Acid Sequence↗
PubMed1987

Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes.

To compare and contrast the human T cell antigen receptor (TcR) alpha and beta chain messages found in human thymocytes to those previously isolated from human peripheral blood T lymphocytes and other nonthymic sources, 13 TcR alpha and 13 TcR beta cDNA were isolated from a human thymocyte library and the nucleotide sequences were determined. The data indicate that, as was found in the peripheral T lymphocytes, the majority of the TcR alpha and TcR beta chain thymocyte cDNA were derived from potentially functional messages. Although the thymocyte-derived TcR cDNA do not contain any unique structural features when compared to TcR cDNA from mature T lymphocytes, 4 new J alpha segments, 17 new V-gene segments (9 V alpha; 8 V beta) and 7 additional V-gene families (4 V alpha and 3 V beta) and sequences had been identified. The exon C beta O, found in many murine thymocyte TcR beta messages, was not found in over 75 human beta chain messages. Based on these new data, a revised estimate of human TcR V alpha, J alpha and V beta repertoires is calculated. The most significant change has been the increase in the estimated number of human TcR V beta-gene segments to a total of about 100 distributed among about 18 families. The V alpha families are now revised upward to 16, with a total number of V alpha segments of 50. The estimate of the J alpha segments in humans remains between 50-100.

Amino Acid Sequence↗
PubMed1987

Genes of the T-cell antigen receptor in normal and malignant T cells.

In this review, the germline genomic and cDNA structures and the evolution of the human TcR-alpha-, TcR-beta-, and Tc gamma-chain genes have been reviewed and discussed. The estimated V-gene segment repertoires established for the human TcR-alpha-, TcR-beta-, and Tc gamma-chain genes have also been summarized. The use of TcR and Tc gamma genes in the evaluation of hematopoietic malignancies and identification of chromosomal translocations has also been presented. It is hoped that such information will serve as a reference point from which the study of TcR genes can further progress. This will almost certainly include the use of TcR and perhaps Tc gamma genes in the study of the dual recognition of antigen and MHC gene products, the role of these genes in thymic education/selection, and the role(s) of these genes in oncogenesis processes and autoimmune settings.

Amino Acid Sequence↗
PubMed1986

Sequences and diversity of human T cell receptor beta chain variable region genes.

The nucleotide sequences of 22 human T cell antigen receptor (TcR) beta chain variable region genes isolated from various T lymphocytes have been analyzed. Of the 19 variable gene segment (V beta)-containing sequences, 17 were unique. The V beta gene segments were grouped into 11 families. Comparisons were made with the data of Concannon et al. to unify the nomenclature. The data is consistent with a total V beta gene segment repertoire with a most probable value of 38 members and an upper bound of 104 members at the 95% confidence level. Southern blot data of germline DNA using selected TcR V beta cDNAs as probes support this estimate. The human repertoire is approximately three to four times greater than that reported for the mouse. Explanations for this discrepancy are proposed.

Base Sequence↗
PubMed1986

Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex.

Human leukemic cells corresponding to the earliest identifiable stages of intrathymic T cell differentiation lack cell surface expression of the T cell receptor(TCR alpha/beta)-T3 complex but transcribe TCR beta mRNA from either germ-line configuration (1/13) or partially (DJ) or fully (VDJ) rearranged (12/13) genes. These cells do not produce TCR alpha mRNA, but do contain T3 delta and T3 epsilon mRNA and accumulate T3 polypeptides, primarily in the perinuclear envelope. Equivalent normal T cells isolated from thymus have a predominantly germ-line configuration of TCR beta but contain intracellular T3 proteins. T3 gene expression is therefore a very early event in T cell differentiation. TCR alpha chain production appears to be the limiting maturation-linked event in the transport, assembly, and cell surface membrane insertion of the TCR alpha/beta-T3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Sequences and repertoire of human T cell receptor alpha chain variable region genes in mature T lymphocytes.

24 human T cell receptor alpha chain messages have been examined by cDNA sequence analysis and Southern blot. The data indicate that there are approximately 40 alpha chain T cell receptor variable gene segments, which can be divided into 12 families. Comparison of the J gene segments from the cDNAs to previously determined germline J alpha sequences places the number of J alpha gene segments over 21, and indicates their number to be approximately 55. Identical nucleotide sequences in independent isolates of V alpha and J alpha gene segments indicate that hypermutation may not be a common mechanism for the expansion of diversity in these genes, and suggest that the major source of diversity within the alpha chain repertoire is a result of recombinational joinings between germline V alpha and J alpha sequences, combined with imprecise junctional joining. Analysis of the V regions of these alpha chain messages reveals the presence of three domains of hypervariability roughly analogous to the CDR1, CDR2, and CDR3 regions of immunoglobulin.

Amino Acid Sequence↗
PubMed1986

T cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia.

The organization and expression of the beta chain of T cell antigen receptor gene (beta-TCR) and Ig H and L chain genes were analyzed by Southern blot technique in 24 patients with a diagnosis of acute myeloblastic leukemia (AML). Rearrangements of the beta-TCR genes were seen in DNA samples from 3 of the 24 patients. One of these three patients also showed rearrangement of the Ig H chain gene. RNA samples from all three patients expressed a beta-TCR gene transcript on dot blot analysis. However, on Northern blot analysis, one patient expressed an incomplete 1.0 kb transcript and no Ig H chain mRNA, despite a rearranged configuration. The karyotypes of two of these patients showed abnormalities involving chromosome 7. Rearrangements of T cell antigen receptor genes may occur in nonlymphoid malignancy, and is consistent with the concept of lineage infidelity in AML.

Adolescent↗
PubMed1986

A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases.

We report here the isolation of a human T cell-specific cDNA clone (YT16) that encodes a protein with extensive homology to a family of transformation and proliferation-related protein-tyrosine kinases (PTK). The message size of YT16 is 2.2 kb and it encodes a protein of 507 amino acids with a mol. mass of 57,136 Daltons. The deduced protein sequence has an overall homology of about 50% to the viral oncogene products of src and yes. Around the PTK catalytic domain, the homologies increase to 70-80% between the deduced protein sequence of YT16 and those of the PTK viral oncogenes. Of special interest is the extensive homology between the deduced protein sequence of YT16 and that of a recently reported murine B and T lymphocyte-specific PTK, lskT. It is possible that YT16 either encodes the human homologue of this murine gene, or a protein with similar function(s) in T cells.

Amino Acid Sequence↗
PubMed1985

Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain.

The organization and sequences of the human beta-chain T-cell receptor diversity, joining, and constant region segments are described. The beta chain of the human T-cell receptor, analogous to the mouse counterpart, consists of two distinct constant region genes approximately equal to 10 kilobases apart. The two constant region genes, C beta 1 and C beta 2, are very similar not only in sequence but also in genomic organization. The coding sequences of each of these C beta constant region genes are divided into four exons. The first two exons encode most of the extracellular constant domain. The third exon encodes a major part of the presumed transmembrane portion, and the last exon contains the cytoplasmic coding sequence as well as 3' untranslated sequences. Except for a stretch of approximately equal to 95 highly conserved nucleotides extending 3' of the first exon of the C region genes, little homology can be found between the intron sequences of C beta 1 and C beta 2. A small cluster of joining region (J beta) gene segments is located approximately equal to 5 kilobases upstream of each of these two constant regions. The first cluster, J beta 1, contains six functional J gene segments while the second, J beta 2, contains seven functional J gene segments. In addition, diversity region (D beta) gene segments are located approximately equal to 600 base pairs upstream of each J beta. Recombinational signals containing highly conserved heptamer and nonamer sequences separated by 12 or 23 bases are found adjacent to all of these D beta and J beta gene segments. These signal sequences are thought to be involved in the somatic recombination processes. These results indicate that what appears to be a gene duplication event giving rise to these two distinct regions must have arisen a long time ago in the evolution of this gene locus.

Base Sequence↗
PubMed1985

Somatic rearrangement of T-cell antigen receptor gene in human T-cell malignancies.

A cDNA clone representing the gene encoding the beta chain of the human T-cell antigen receptor has been isolated recently. By using fragments of this cDNA as hybridization probes in Southern blot analysis of restriction endonuclease-digested genomic DNA, we have now examined the structure of the gene in DNA from 26 patients with acute leukemia and from 23 normal individuals. We have found that the T-cell antigen receptor gene has undergone somatic rearrangement in 14 of 14 patients with the phenotypic diagnosis of T-cell acute lymphoblastic leukemia. In this group of patients, similar patterns of rearrangement appear to occur in different patients. This finding suggests that there is either a limited repertoire of possible rearrangements or an association between the development of leukemia and specific patterns of rearrangement. DNA from 6 patients with acute myeloblastic leukemia, 6 patients with non-B, non-T acute lymphoblastic leukemia, and 23 nonleukemic individuals showed no rearrangement or polymorphism. One case of T-cell acute lymphoblastic leukemia, however, showed rearrangement of both the T-cell receptor beta chain and the constant region of the immunoglobulin gene. Studies with mixtures of DNAs from leukemic bone marrow cells and cultured skin fibroblasts, as well as with remission and relapse marrow DNAs from the same patients, indicate that this technique can detect 1% leukemic cells in a mixed population. In addition, DNA from the marrow of a patient in relapse contains a similar rearrangement to that found in the marrow sample taken at the time of diagnosis, which suggests that the original clone of leukemic cells was responsible for relapse. Our results indicate that assessment of rearrangement of the T-cell antigen receptor gene will be valuable in the diagnosis and management of leukemia and can be used to evaluate clonality in T-cell neoplasia.

Chromosome Mapping↗
PubMed1985

Genes encoding the T-cell antigen receptor.

The search for the elusive and controversial T-cell antigen receptor is over. It is now clear that gene complexes for both alpha and beta chains are distinct from those for immunoglobulin genes. They are, however, related to Ig genes as well as to other class I and class II major histocompatibility complex (MHC) gene products. Therefore, they belong to the immunoglobulin super gene family.

DNA, Circular↗
PubMedDate not supplied

Rearrangements of T-cell receptor gene YT35 in human DNA from thymic leukaemia T-cell lines and functional T-cell clones.

An essential property of the immune response is its ability to distinguish between self and non-self and to generate enormous diversity in antibody and T-cell immune responses. Although the genetic and molecular mechanisms responsible for antibody diversity have now largely been elucidated, the structure of the T-cell receptor and the diversification of the receptor repertoire have only recently become amenable to study. One approach has involved immunochemical studies of the protein precipitated by monoclonal antibodies which react specifically with the immunizing T-cell clones. Another approach has been to clone and sequence a human or a murine T-cell specific message that may specify part of the T-cell receptor. We present here results of Southern blot analysis of non-T, immature T, and mature T-cell genomic DNA, and provide evidence that rearrangements of the YT35 sequences do occur in the DNA of thymic leukaemia T cells. This suggests that YT35 codes for at least part of the T-cell receptor and that rearrangements occur at this early stage of thymic ontogeny. Furthermore, DNA rearrangements are present in lymphocytes with phenotypic and functional characteristics of helper, killer, or suppressor T cells. We conclude that the three subpopulations of T cells operate via receptor molecules encoded by the same gene family.

Cell Line↗
PubMedDate not supplied

Gene rearrangement in cells with natural killer activity and expression of the beta-chain of the T-cell antigen receptor.

The mammalian host defence system can be divided broadly into adaptive and non-adaptive immunity. Adaptive immunity is acquired and is mediated by B and T lymphocytes. Non-adaptive immunity is mediated in part by a small subclass of heterogeneous peripheral blood mononuclear cells. This population, termed null cells, consists of haematopoietic precursors and cells mediating natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC). NK cells are a class of non-adherent, non-phagocytic, rapidly cytotoxic lymphocytes which can efficiently lyse a wide variety of tumour cells, virally infected cells and immature cell types of normal origin. Despite the broad range of targets, only a limited number of specificities are thought to be involved in target-cell recognition. Morphologically, NK cells are large granular lymphocytes, but they have been shown to exhibit cell-surface markers characteristic of both T cells and monocytes, raising doubt over their lineage. The recent cloning of the beta-chain of the T-cell antigen receptor has now allowed us to investigate whether some NK cells are T-cell-related. We have examined rearrangement and expression of the beta-chain of the T-cell receptor in cloned murine NK cell lines and fresh murine NK cell populations, and our results support the hypothesis that a subpopulation of NK cells is related to T cells and provide basis for examining whether some NK activity is mediated by a small number of T-cell receptors.

Animals↗