Regulation of T-cell receptor gene expression in human T-cell development.

Collins, Mary; Tanigawa, G; Kissonerghis, A.-M.; Ritter, M A; Price, Karen M.; Tonegawa, Susumu; Owen, Michael John

doi:10.1073/pnas.82.13.4503

Cited by 61 publications

(15 citation statements)

References 24 publications

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“…In murine fetal tissue, TCR-,y transcription precedes transcription of TCR-# and TCR-a, thereafter, it decreases in inverse proportion to TCR-a transcription during thymic development (21)(22)(23)(24)(25)(26). In this study, however, most of stage III and IV T-ALL had TCR-'y transcripts.…”

Section: Resultscontrasting

confidence: 45%

“…Thereafter, during further differentiation, transcription of the TCR-y gene decreases, while TCR-a transcription increases (21)(22)(23)(24)(25)(26). Moreover, as shown in T-ALL cells, the CD3 proteins can combine with TCR-,B protein in the cytoplasm of CD3-immature cells, whereas TCR-a transcripts and protein have only been observed in CD3+ cells (27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, as shown in T-ALL cells, the CD3 proteins can combine with TCR-,B protein in the cytoplasm of CD3-immature cells, whereas TCR-a transcripts and protein have only been observed in CD3+ cells (27)(28)(29)(30). Expression ofthe TCR-a gene may thus serve as the critical regulatory event in the formation of the CD3-Ti complex at the cell surface (26 Southern blot hybridization. High molecular weight DNA was prepared from mononuclear cells and digested with appropriate restriction endonucleases.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

Hara¹,

Benedict²,

Champagne³

et al. 1988

J. Clin. Invest.

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Section: Resultscontrasting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

Hara¹,

Benedict²,

Champagne³

et al. 1988

J. Clin. Invest.

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“…Studies using MOLT-4 T-cell leukemia cells reveal the presence of intracellular 8, y, and E chains but no cell surface expression (23,24). These cells have P-chain transcripts but lack mRNA for the a chain (25). The reports of the existence of surface 8 chain in the absence of a-/ heterodimer in a subset of human T cells are of particular interest (26).…”

Section: Resultsmentioning

confidence: 99%

Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.

Minami¹,

Weissman²,

Samelson³

et al. 1987

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

221

154

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The murine T-cell antigen receptor consists of at least seven chains and six different proteins. The two clonotypic chains a and fi are glycoproteins of 40-45 kDa present as a disulfide-linked heterodimer. Four clonally invariant chains include 8 (a 26-kDa glycoprotein), y (a 21-kDa glycoprotein), e (a 25-kDa protein), and C (a 16-kDa protein).{is found in the complex as a disulfide-linked homodimer. The clonotypic chains and the invariant chains form a noncovalent complex on the cell surface. We have developed antibodies against each of the chains and used them to examine the assembly of the mature complex in the murine antigen-specific T-cell hybridoma 2B4. Pulse-chase studies of metabolically labeled cells demonstrate that many of the chains are synthesized in great excess over the amount assembled into the mature complex. These excess chains, either as free components or as partially assembled complexes, are rapidly degraded. This degradation most likely takes place in the lysosomes. The complete complex is quite stable with a long half-life. A specific hierarchy of partially assembled complexes can be discerned.Numerous cell surface receptors are multisubunit complexes including the acetylcholine receptor, the IgE Fc receptor, and the T-cell antigen receptor. The complete and precise assembly ofthese components is a formidable problem, but one that has been solved by the cell to ensure proper function of these critical cellular elements. In studies of the acetylcholine receptor (1, 2), it was established that only about 30o of the newly synthesized a chain is assembled into mature receptor. The unassembled a chains are rapidly degraded (1, 2). A similar set of observations about the B-cell antigen receptor (surface IgM) has correlated assembly of multisubunit complexes with dramatic stabilization of the components of the complexes (3). Studies of the assembly of erythrocyte cytoskeletal proteins, a and , spectrin, revealed that unassembled chains were rapidly degraded, in contrast to the fully assembled complex (4). The selective stabilization imparted by complex assembly may be critical to the mechanism whereby the cell ensures the existence of only stoichiometrically assembled protein complexes.Because selective catabolism may be fundamental to the selective survival of properly assembled complexes, the cell must possess mechanisms whereby unassembled, partially assembled, or incorrectly assembled complexes can be recognized. The following two major systems for intracellular proteolysis have been extensively studied: lysosomes and cytosolic ATP-dependent proteolytic pathways. Degradation by each of these is selective. Lysosomes are generally regarded as the major site of degradation of membrane proteins but they can also be responsible for the catabolism of cytosolic proteins and the content of other intracellular organelles (5). ATP-dependent, cytosolic, neutral protease systems have been implicated in the selective degradation of cytosolic proteins (6). Denatured proteins when microinjected into...

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“…T3-Ti expression is noted only in the most mature thymocytes and peripheral T cells (7,8). The human I TCR gene is located on chromosome 7 at band q35 (9) and is comprised oftwo constant (Cal) segments, 13 joining (Jo) segments, two or more diversity (Do) segments, and -100 variable (VO) gene segments (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.

Felix¹,

Wright²,

Poplack³

et al. 1987

J. Clin. Invest.

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We examined a-, ,(-, and 'y-T cell receptor (TCR) gene activation within acute lymphoblastic leukemias (ALLs) that represent early stages of B and T cell development. We wished to determine if TCR rearrangement and expression was lineage restricted, showed any developmental hierarchy, or could identify new subsets of T cells. Rearrangement of 'y and , ( TCR genes occurred early in development but in no set order, and most T-ALLs (22/ 26) were of sufficient maturity to have rearranged both genes.T-ALLs preferentially rearranged C.y2 versus the Cj1 complex; no preference within thef( locus was apparent. Once rearranged, the TCR continued to be expressed (11/13), whereas the y TCR was rarely expressed (3/14). The a TCR was expressed only in more mature T-ALLs (8/14) that usually displayed T3. The 3A-1 T cell associated antigen appeared earliest in development followed by T111 and T3. Within pre-B cell ALL a higher incidence of lineage spillover was noted for y TCR rearrangements (8/17) than for rearrangements (3/17). This also contrasts with the only occasional rearrangement of immunoglobulin (Ig) heavy chains (3/25) in T-ALL. However, in pre-B ALL the pattern of y TCR usage was distinct from that of T cells, with the C,1 complex utilized more frequently. Almost all ALLs could be classified as pre-B or T cell in type by combining Ig and TCR genes with monoclonal antibodies recognizing surface antigens, although examples of lineage duality were noted. Unique subpopulations of cells were discovered including two genetically uncommitted ALLs that failed to rearrange either Ig or TCR loci. Moreover, two T lymphoblasts were identified that possessed the T3 molecule but failed to express a plus , ( TCR genes. These T-ALLs may represent a fortuitous transformation of T cell subsets with alternative T3-Ti complexes.

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Regulation of T-cell receptor gene expression in human T-cell development.

Cited by 61 publications

References 24 publications

Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

Comparison of T cell receptor alpha, beta, and gamma gene rearrangement and expression in T cell acute lymphoblastic leukemia.

Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.

T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.

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