Promoter Element for Transcription of Unrearranged T-Cell Receptor β-Chain Gene in Pro-T Cells

The hallmark of T- and B-lymphocyte development is the rearrangement of variable (V), diversity (D), and joining (J) segments of T-cell receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse repertoire of antigen receptor specificities in the immune system. The process of V(D)J recombination is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibility to the recombinase apparatus in a lineage- and stage-specific manner. These chromatin changes are linked to transcription of the locus in its unrearranged (germline) configuration. To understand how germline transcription of the TCRβ-chain gene is regulated, we determined the structure of germline transcripts initiating near the Dβ1 segment and identified a promoter within this region. The Dβ1 promoter is active in the presence of the TCRβ enhancer (Eβ), and in this context, exhibits preferential activity in pro-T versus mature T-cell lines, as well as T- versus B-lineage specificity. These studies provide insight into the developmental regulation of TCRβ germline transcription, one of the earliest steps in T-cell differentiation.

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Promoter Element for Transcription of Unrearranged T-Cell Receptor β-Chain Gene in Pro-T Cells

Blood ◽

10.1182/blood.v93.9.3017 ◽

1999 ◽

Vol 93 (9) ◽

pp. 3017-3025 ◽

Cited By ~ 28

Author(s):

Raymond T. Doty ◽

Dong Xia ◽

Suzanne P. Nguyen ◽

Tanya R. Hathaway ◽

Dennis M. Willerford

Keyword(s):

T Cell ◽

T Cell Receptor ◽

B Lymphocyte ◽

Developmental Regulation ◽

Antigen Receptor ◽

Cell Receptor ◽

Chain Gene ◽

Germline Transcription ◽

Lineage Specificity ◽

T Cell Lines

Abstract The hallmark of T- and B-lymphocyte development is the rearrangement of variable (V), diversity (D), and joining (J) segments of T-cell receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse repertoire of antigen receptor specificities in the immune system. The process of V(D)J recombination is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibility to the recombinase apparatus in a lineage- and stage-specific manner. These chromatin changes are linked to transcription of the locus in its unrearranged (germline) configuration. To understand how germline transcription of the TCRβ-chain gene is regulated, we determined the structure of germline transcripts initiating near the Dβ1 segment and identified a promoter within this region. The Dβ1 promoter is active in the presence of the TCRβ enhancer (Eβ), and in this context, exhibits preferential activity in pro-T versus mature T-cell lines, as well as T- versus B-lineage specificity. These studies provide insight into the developmental regulation of TCRβ germline transcription, one of the earliest steps in T-cell differentiation.

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Germ-line configuration of the T-cell receptor beta-chain gene in B-cell chronic lymphoproliferative disorders which co-express T-cell antigens

European Journal Of Haematology ◽

10.1111/j.1600-0609.1987.tb01448.x ◽

2009 ◽

Vol 39 (5) ◽

pp. 412-417 ◽

Cited By ~ 4

Author(s):

Fortunato Morabito ◽

Angela Tassinari ◽

Vincenzo Callea ◽

Maura Brugiatelli ◽

Maria Teresa Fierro ◽

...

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Germ Line ◽

Cell Receptor ◽

Lymphoproliferative Disorders ◽

Chain Gene ◽

Line Configuration ◽

T Cell Antigens ◽

T Cell Receptor Beta ◽

Receptor Beta

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Analysis of Function, Specificity and T Cell Receptor Expression of Cloned Mucosal T Cell Lines in Crohn's Disease

Journal of Autoimmunity ◽

10.1006/jaut.1996.0023 ◽

1996 ◽

Vol 9 (2) ◽

pp. 193-204 ◽

Cited By ~ 14

Author(s):

Thomas P. Prindiville ◽

Mary C. Cantrell ◽

Takayuki Matsumoto ◽

William R. Brown ◽

Aftab A. Ansari ◽

...

Keyword(s):

Crohn’S Disease ◽

T Cell ◽

Crohn's Disease ◽

T Cell Receptor ◽

Cell Lines ◽

Cell Receptor ◽

Receptor Expression ◽

T Cell Lines ◽

Analysis Of Function

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T-cell receptor variable region of the β-chain gene use in peripheral blood and multiple synovial membranes during rheumatoid arthritis

Human Immunology ◽

10.1016/0198-8859(94)00121-6 ◽

1995 ◽

Vol 42 (4) ◽

pp. 331-339 ◽

Cited By ~ 21

Author(s):

Antoine Alam ◽

Jacqueline Lulé ◽

Héléne Coppin ◽

Nathalie Lambert ◽

Bernard Maziéres ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

T Cell Receptor ◽

Peripheral Blood ◽

Variable Region ◽

Cell Receptor ◽

Chain Gene ◽

Synovial Membranes ◽

Β Chain

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Angioimmunoblastic T-Cell Lymphoma With Cutaneous Involvement: A Case Report With Subtle Histologic Changes and Clonal T-Cell Proliferation

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-e122-atlwci ◽

2004 ◽

Vol 128 (10) ◽

pp. e122-e124

Author(s):

Chien-Tai Huang ◽

Shih-Sung Chuang

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Gene Rearrangement ◽

Cell Lymphoma ◽

Paraffin Section ◽

Cell Receptor ◽

T Cell Lymphoma ◽

Chain Gene ◽

Angioimmunoblastic T Cell Lymphoma ◽

Lymphoid Infiltrate

Abstract Angioimmunoblastic T-cell lymphoma is a nodal peripheral T-cell lymphoma that rarely involves the skin. We describe a 62-year-old Taiwanese man who developed a second relapse of angioimmunoblastic T-cell lymphoma with generalized erythroderma and numerous plaquelike and nodular lesions. Biopsy of the erythematous skin lesion demonstrated mild infiltrate of atypical small lymphocytes, some with clear cytoplasm. The lymphoid infiltrate was located mainly around skin appendages and in the upper dermis without epidermotropism. Immunohistochemically, these atypical lymphocytes expressed CD3. Polymerase chain reaction analysis for T-cell receptor γ-chain gene rearrangement using paraffin section showed the same-sized monoclonal bands in the skin and 2 previous nodal biopsies. We conclude that the histologic features of angioimmunoblastic T-cell lymphoma involving skin may be very subtle, showing only mild lymphoid infiltrate. Awareness of the history of angioimmunoblastic T-cell lymphoma with ancillary studies, including clonality testing for T-cell receptor gene rearrangement, is crucial for reaching an accurate diagnosis.

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Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor

Molecular and Cellular Biology ◽

10.1128/mcb.14.2.1095-1103.1994 ◽

1994 ◽

Vol 14 (2) ◽

pp. 1095-1103

Author(s):

A L Burkhardt ◽

T Costa ◽

Z Misulovin ◽

B Stealy ◽

J B Bolen ◽

...

Keyword(s):

Signal Transduction ◽

T Cells ◽

T Cell ◽

B Cell ◽

T Cell Receptor ◽

Interleukin 2 ◽

Antigen Receptor ◽

Cell Receptor ◽

Antigen Receptors ◽

Cell Antigen

Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T-cell receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have studied signal transduction by chimeric immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin-2 secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.

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