Studies of the mouse Ly-6 alloantigen system

Kimura, Shoji; Tada, Nobuhiko; Liu-Lam, Yen; Hämmerling, Ulrich

doi:10.1007/bf00373446

Cited by 93 publications

(48 citation statements)

References 21 publications

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“…As shown in Table 1 the strain distribution of expression for both antigens is tightly linked to the Ly-6 locus (15)(16)(17)(18). To confirm this observation, we stained T cells from the congeneic strain C3H.B6-Ly-6b.…”

Section: Resultsmentioning

confidence: 71%

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Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus.

Reiser

Yeh²,

Gramm

et al. 1986

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

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Recently we described two murine T-cell membrane proteins, TAP (T-cell-activating protein) and TAPa (TAP-associated protein). Previous experiments suggested that TAP is involved in physiologic T-cell activation. The subject of this report is a genetic analysis of these molecules. TAP and TAPa map to the Ly-6 locus. The relationship of these molecules to other antigens encoded in this locus is examined. Based on tissue distribution, molecular structure, and functional properties, TAP is distinct from any previously described Ly-6 antigen, whereas TAPa is probably identical to the 34-11-3 antigen. TAP and TAPa are coexpressed on all cell types examined so far. Moreover, comparative studies demonstrate a complex developmentally regulated pattern in the expression of molecules encoded in this locus.

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Section: Resultsmentioning

confidence: 71%

“…By NaDodSO4/PAGE it has an apparent molecular mass of 10-12 kDa, which increases upon reduc--68 tion, suggesting the presence of internal disulfide bridges. (18,20). This antigen has a very similar cell distribution to TAP and TAPa/34-11-3.…”

Section: Discussionmentioning

confidence: 90%

Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus.

Reiser

Yeh²,

Gramm

et al. 1986

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

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“…For this purpose, we included the mAbs 34-11-3 (37), 2D7 (6), and S8.106, the latter antibody directed against the Ly-6A epitope defined by Kimura et al (11). It was quite surprising to us that the mAbs 2D7 and 34-11-3 also recognized the product of the transfected Ly-6 cDNA because previous biochemical analysis had suggested that these mAbs are directed against a distinct antigen, provisionally termed TAPa because of the coexpression of this antigen with the TAP molecule (6, 8-10).…”

Section: Resultsmentioning

confidence: 99%

“…A polymorphism in the expression of TAP in inbred mouse strains, matches precisely that of the "b" haplotype of the Ly-6 locus. This locus, which consists of two haplotypes, Ly-6.J (Ly-6a) and Ly-6.2 (Ly-6b), encodes multiple lymphoid antigens (8,11).…”

mentioning

confidence: 99%

Cloning and expression of a cDNA for the T-cell-activating protein TAP.

Reiser

Coligan

Palmer

et al. 1988

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

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The T-cell-activating protein TAP is a murine phosphatidylinositol-anchored glycoprotein whose expression is controlled by the Ly-6 locus. Previous studies have suggested an important role for this protein in physiological T-cell activation. Using oligonucleotide probes, we have now isolated a cDNA clone whose predicted sequence would encode a protein with an NH2-terminal sequence identical to that of the TAP molecule. Further analysis of the predicted protein sequence revealed a cysteine-rich protein with a hydrophobic domain at the COOH terminus and without N-linked glycosylation sites-all features consistent with our previous analysis of the TAP protein. In Southern blot analysis, the Ly-6.2 cDNA clone detects a multigene family and a restriction fragment length polymorphism that maps precisely to the Ly-6 locus. Expression of the cDNA clone in COS cells demonstrates that it codes for TAP and clarifies the relationship between the epitopes recognized by various aLy-6 monoclonal antibodies.Finally, we have studied the expression of Ly-6 mRNA in a variety of cell lineages. Ly-6 transcripts were detected in all organs examined, including spleen, kidney, lung, brain, and heart. This demonstrates that the Ly-6 locus is transcriptionally active in a wide range of organs and suggests that the role of TAP or TAP-like proteins might extend to other tissues.Activation of T inducer cells is antigen-dependent and major histocompatibility complex (MHC)-restricted (1). The specificity of activation is imparted by a clonotypic receptor, composed of two variable protein chains, Ti a and ,B (2, 3). Cell-surface expression of the T-cell receptor (TCR) has been extensively characterized. It requires coexpression of a set of nonpolymorphic proteins, termed T3, which are physically associated with the antigen receptor (4, 5). In contrast, the molecular mechanisms of signal transduction after TCR triggering is not understood.Recent findings by our laboratory have raised the possibility that the T-cell-activating protein (TAP) (6), a phosphatidylinositol-anchored, murine glycoprotein (7), is involved in this process: First, antibodies against TAP can induce T-cell proliferation and can augment stimulation of the TCR (6). Second, TAP is expressed on virtually all L3T4+ peripheral T cells, and in the thymus, TAP expression defines the immunocompetent compartment (8-10). Finally, T-cell-T-cell (T-T) hybridoma mutants that are deficient in the expression of TAP have significant defects in their responsiveness to TCR stimulation (33).The gene encoding the TAP molecule maps to the Ly-6 locus (8). A polymorphism in the expression of TAP in inbred mouse strains, matches precisely that of the "b" haplotype of the Ly-6 locus. This locus, which consists of two haplotypes, Ly-6.J (Ly-6a) and Ly-6.2 (Ly-6b), encodes multiple lymphoid antigens (8, 11).We have previously reported the nearly complete NH2-terminal sequence of the TAP molecule (12). Based on the obtained protein sequence data, oligonucleotides were synthesized and used to sc...

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“…We do not know whether SET-CAN was also expressed in the stomach mucosa of the other transgenic lines because they were no longer available for analysis. Because no expression of Ly6E.1/ScaI was reported in studies that analyzed the presence of this protein in other mouse tissues, 39,40 it is possible that the mucosal expression in line 2969 is ectopic and is the result of the transgene integration site.…”

Section: Discussionmentioning

confidence: 99%

SET-CAN, the Product of the t(9;9) in Acute Undifferentiated Leukemia, Causes Expansion of Early Hematopoietic Progenitors and Hyperproliferation of Stomach Mucosa in Transgenic Mice

Özbek

Kandilci

Baal

et al. 2007

The American Journal of Pathology

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Leukemia-specific chromosome translocations involving the nucleoporin CAN/NUP214 lead to expression of different fusion genes including DEK-CAN, CAN-ABL, and SET-CAN. DEK-CAN and CAN-ABL1 are associated with acute myeloid leukemia and T-cell acute lymphoblastic leukemia, respectively, whereas SET-CAN was identified in a patient with acute undifferentiated leukemia. In addition, SET is overexpressed in solid tumors of the breast, uterus, stomach, and rectum. Ectopic expression of SET-CAN inhibits vitamin-D 3 -induced differentiation of the human promonocytic U937cells, whereas ectopic SET expression induces differentiation. Here, we assessed the leukemogenic potential of SET-CAN in the hematopoietic system of transgenic mice. Although SET-CAN mice showed expansion of an early progenitor cell pool and partial depletion of lymphocytes, the animals were not leukemia-prone and did not show shortening of disease latency after retroviral tagging. This suggests that SET-CAN expression in acute undifferentiated leukemia might determine the primitive phenotype of the disease, whereas secondary genetic lesions are necessary for disease development. Leukemia-specific chromosome translocations frequently lead to the formation of chimeric genes encoding fusion proteins. Many of these translocations result in the expression of altered transcription factors that are thought to induce aberrant expression of crucial target genes and thereby contribute to the dysregulated growth of hematopoietic progenitors.1 Translocations are associated with specific leukemia subtypes, suggesting that the in vivo oncogenicity of the encoded fusion proteins shows high specificity within the hematopoietic system.The translocation t(6;9)(p23;q34) is mostly associated with the M2/M4 subtype of acute myeloid leukemia and is characterized by a poor prognosis and a young age of onset.2,3 On chromosome 9, breakpoints occur in a specific intron, icb-9, of the nucleoporin CAN/NUP214, a protein essential for nucleocytoplasmic transport and cell-cycle progression.4,5 CAN/NUP214 is also targeted by the t(9;9)(q32;q34) in a case of acute undifferentiated leukemia (AUL), generating a fusion gene with SET. Recently, the same fusion was reported in a patient with acute myeloid leukemia. 6 This chimeric gene consists of nearly the entire SET coding sequence fused to the Cterminal two thirds of CAN/NUP214 and encodes a protein of 155 kd.

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Studies of the mouse Ly-6 alloantigen system

Cited by 93 publications

References 21 publications

Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus.

Gene encoding T-cell-activating protein TAP maps to the Ly-6 locus.

Cloning and expression of a cDNA for the T-cell-activating protein TAP.

SET-CAN, the Product of the t(9;9) in Acute Undifferentiated Leukemia, Causes Expansion of Early Hematopoietic Progenitors and Hyperproliferation of Stomach Mucosa in Transgenic Mice

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