Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain a better understanding of the organization of the complex T-cell antigen receptor alpha/delta (TCR alpha/delta) locus, a deletional analysis using the known six variable (V) regions of the TCR delta was performed in informative leukemic cell lines and fresh leukemias. We and others have previously reported a high incidence of V delta 2-(D)-D delta 3 rearrangements in non-T, non-B-lymphoid precursor acute lymphocytic leukemia (LP-ALL). In contrast V delta 4, V delta 5, V delta 6 rearrangements were rare or absent. V delta-J alpha rearrangements were found in LP-ALL and in T-ALL. Our deletion and rearrangement data combined with that of others suggest the following 5' to 3' organization of the TCR alpha/delta locus: V delta 6-(V delta 4-V alpha 1.2)-V alpha 12.1-V alpha 13.1-V delta 1-V delta 17.1-V delta 5-delta Rec-V delta 2-D/J/C delta-V delta 3-TEA-psi J alpha-J alpha G. The frequency of rearrangements of the various V delta genes suggests preferential use of the V delta most proximal to D/J delta.
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PMID:Organization of the T-cell receptor delta locus by deletional analysis of acute lymphoblastic leukemias and leukemic cell lines. 183 1

The nested location of the TCR-delta gene within the TCR-alpha locus is a common feature of both mouse and human. Yet alpha/beta and gamma/delta T cells represent two separate lineages. We have previously proposed that a specific rearrangement event (delta Rec--psi J alpha) resulting in the specific deletion of the TCR-delta gene could be responsible for the independent usage of these two loci. We used an in vitro model of T cell differentiation to test this hypothesis. We show that in culture conditions (IL-1 + sCD23) which promote the development of alpha/beta expressing T cells exclusively, the specific deletion of the TCR-delta locus occurs very rapidly, probably before the productive rearrangement of the TCR-alpha gene. These results clearly demonstrate that the specific deletion of the TCR-delta gene could be the initial regulatory event that imprints the irreversible commitment of T cell differentiation along the alpha/beta pathway.
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PMID:The differentiation of human pro-thymocytes along the TCR-alpha/beta pathway in vitro is accompanied by the site-specific deletion of the TCR-delta locus. 183 4

It has been hypothesized that a rearrangement between the delta recombining element (delta Rec) and a pseudo J alpha gene serves to delete the TCR-delta locus before rearrangement of the TCR-alpha genes. We have now sequenced a direct, site-specific rearrangement between the delta Rec element and a pseudo J alpha gene in a human leukemic stem-cell line. Putative "N-sequence" addition was noted at the site of recombination, suggesting that this event occurred at a time when the enzyme(s) involved in N-region addition were active in this cell. This provides support for the view that deletion of the TCR-delta locus is required before rearrangement of the TCR-alpha chain genes.
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PMID:Demonstration of delta rec-pseudo J alpha rearrangement with deletion of the delta locus in a human stem-cell leukemia. 274 62

V delta 3 usage and combinatorial expression of V gamma and V delta regions was studied on peripheral T cells with a novel V delta 3-specific mAb (p11.10b), generated against a soluble V gamma 9V delta 3 TCR. V delta 3+ cells represented the vast majority of V delta 1/V delta 2- gamma delta T cells within peripheral blood and mucosal lymphocytes. No preferential V gamma region expression was noted within V delta 3+ cells, but the frequency of V gamma 9+ cells was significantly lower among V delta 3+ than among V delta 1+ or V delta 2+ PBL. Phenotypic analysis of cultured V delta 3+ cells sorted with p11.10b mAb revealed the presence of T lymphocytes with unusual phenotypes. First, cells carrying two distinct surface TCR delta-chains, recognized by both V delta 1- and V delta 3-specific mAbs, were detected in most T cell lines, though at frequencies much lower than that of dual gamma expressors, indicating that allelic exclusion of delta genes is more tightly regulated than that of gamma genes. Moreover, a significant fraction of V delta 3+ cells were recognized by C beta- but not C delta-specific mAbs. Molecular analysis of V delta 3+C beta+ clones revealed the presence of V delta 3J alpha C alpha transcripts in all of them. Given the peculiar location of the V delta 3 gene between the delta Rec/psi J alpha elements, those observations formally demonstrate that activation of rearrangements with J alpha elements is not necessarily preceded by a delta Rec/psi J alpha-mediated deletion of the delta locus on the same chromosome.
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PMID:Repertoire analysis of human peripheral blood lymphocytes using a human V delta 3 region-specific monoclonal antibody. Characterization of dual T cell receptor (TCR) delta-chain expressors and alpha beta T cells expressing V delta 3J alpha C alpha-encoded TCR chains. 767 22

The spontaneously hypertensive rat (SHR) is a stress-sensitive animal which exhibits moderate immune dysfunction that has been implicated in the onset of hypertension. In this study, we examined the morphology of SHR thymus and spleen and further characterized the immune deficiency using Wistar-Kyoto (WKY) and Fisher 344 (F-344) rats for comparison. The adult SHR thymus does not display the increase in medullary volume typically noted with aging and the volume density of the marginal zone is decreased in the spleen. In vivo tritiated-thymidine incorporation is also decreased in the spleen of unstimulated SHR. In mixed lymphocyte reactions (MLR), the proliferative response of SHR splenocytes is significantly decreased relative to controls, WKY and F-344. Addition of interleukin-1 (IL-1), interleukin-2 (IL-2), or indomethacin to the MLR cultures does not increase proliferation. The proliferative response to T cell receptor monoclonal antibody (mAb-TCR) or interleukin-2 (IL-2) are similarly impaired in the SHR. The depressed proliferative T cell response is reversed by prolactin. It is suggested that the SHR is a valuable model for the study of immune deficiency.
Anat Rec 1993 Oct
PMID:Immune system of the spontaneously hypertensive rat: II. Morphology and function. 823 75

The genetic element 'T early alpha' (TEA) in humans is located immediately 5' to the most upstream joining segment (phi J alpha) of the TCR alpha chain locus. The TEA transcript is present early in thymocyte ontogeny and the TEA-associated deletion of the TCR delta locus (delta Rec/phi J alpha rearrangement) precedes V alpha/J alpha rearrangement. We detected a 1.8 kb transcript homologous to human TEA that is spliced to C alpha in mouse thymic lymphomas showing concomitant rearrangement and expression of TCR gamma, delta, beta, and alpha. The TEA expression was highest in day 17 fetal thymocytes and declined thereafter. This expression parallels the TCR delta gene expression which is preceded by TCR gamma expression, and followed by the expression of TCR beta and alpha genes.
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PMID:Mouse germline transcript of TCR alpha joining region and temporal expression in ontogeny. 838 95

The TCR is a heterodimeric molecule composed of either gamma delta or alpha beta chains. The differentiation mechanisms that force thymocytes into the gamma delta alpha beta lineage are poorly understood, but rearrangement processes in the TCR-delta alpha locus are likely to play an important role. The TCR-delta gene complex is flanked by the delta-deleting elements delta Rec and psi J alpha, which are assumed to delete the TCR-delta gene before V alpha-J alpha rearrangement. The nonproductive delta Rec-psi J alpha recombination occurs at high frequency in both fetal and postnatal immature thymocytes. To find DNA binding proteins involved in the delta Rec-psi J alpha preferential rearrangement, we performed electrophoretic mobility shift assays using the recombination signal sequence of psi J alpha with additional upstream and downstream sequences. We observed a 180-kDa DNA binding protein in nuclear extracts from human thymocytes that recognized a 46-bp binding site on the psi J alpha gene segment, containing the core motif GTTAATAGG. The psi J alpha binding protein, which we call PJA-BP, was also detected in immature CD3-T cell lines with TCR-delta genes deleted on both alleles, in a TCR-alpha beta+ cell line, and in two of four myeloid cell lines. This protein was absent in a TCR-gamma delta+ T cell line, in nonhemopoietic cell lines, and in all but one B cell lines tested. Although we could detect binding activity of the PJA-BP to some other TCR-J alpha gene segments, we postulate that binding of PJA-BP to the psi J alpha gene segment is one of the factors involved in the preferential delta Rec-psi J alpha gene rearrangement process.
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PMID:A DNA binding protein in human thymocytes recognizes the T cell receptor-delta-deleting element psi J alpha. 862 17

R73, a monoclonal antibody that recognizes a rat T cell surface antigen of TCR(alphabeta), was used to identify thymocytes that express major histocompatibility complex-restricted antigen receptors, and to define the spatial relation between these receptor-bearing thymocytes and individual thymic cortical and medullary epithelial subtypes by ultrastructural immunohistochemistry. We show that in both the cortex and medulla 1) the thymocytes that reacted with R73 antibodies exhibited three staining patterns: cytoplasmic-only staining, simultaneous cytoplasmic and surface membrane staining, and surface membrane-only staining; 2) the subcapsular/perivascular epithelial cells (ECs) were usually associated with thymocytes expressing perinuclear staining only; and 3) the surface membrane areas of thymocytes that expressed antigen receptors made contact with pale and intermediate ECs, but not with dark cells. These results suggest that thymic selection of major histocompatibility complex restriction and/or tolerance may occur by interaction of the receptors on maturing thymocytes with major histocompatibility complex antigens on thymic ECs in general, and on pale and intermediate subtypes in particular.
Anat Rec 2002 Jun 01
PMID:Spatial relation between major histocompatibility complex-restricted antigen receptor-bearing thymocytes and subtypes of thymic epithelial cells. 1199 81