scholarly journals V beta 17 T-cell deletion by endogenous mammary tumor virus in wild-type-derived mouse strain.

1992 ◽  
Vol 89 (8) ◽  
pp. 3232-3235 ◽  
Author(s):  
E. Jouvin-Marche ◽  
P. A. Cazenave ◽  
D. Voegtle ◽  
P. N. Marche
Keyword(s):  
T Cell ◽  
Mammary Tumor ◽  
Mouse Strain ◽  
Wild Type ◽  
Mammary Tumor Virus ◽  
Tumor Virus ◽  
Cell Deletion

scholarly journals Peripheral T cell activation and deletion induced by transfer of lymphocyte subsets expressing endogenous or exogenous mouse mammary tumor virus.

1993 ◽  
Vol 177 (5) ◽  
pp. 1359-1366 ◽  
Author(s):  
G A Waanders ◽  
A N Shakhov ◽  
W Held ◽  
O Karapetian ◽  
H Acha-Orbea ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Lymphocyte Subsets ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Cell Deletion

Murine T cell reactivity with products of the minor lymphocyte stimulatory (Mls) locus correlates with the expression of particular variable (V) domains of the T cell receptor (TCR) beta chain. It was recently demonstrated that Mls antigens are encoded by an open reading frame (ORF) in the 3' long terminal repeat of either endogenous or exogenous mouse mammary tumor virus (MMTV). Immature thymocytes expressing reactive TCR-V beta domains are clonally deleted upon exposure to endogenous Mtv's. Mature T cells proliferate vigorously in response to Mls-1a (Mtv-7) in vivo, but induction of specific anergy and deletion after exposure to Mtv-7-expressing cells in the periphery has also been described. We show here that B cells and CD8+ (but not CD4+) T cells from Mtv-7+ mice efficiently induce peripheral deletion of reactive T cells upon transfer to Mtv-7- recipients, whereas only B cells stimulate specific T cell proliferation in vivo. In contrast to endogenous Mtv-7, transfer of B, CD4+, or CD8+ lymphocyte subsets from mice maternally infected with MMTV(SW), an infectious homologue of Mtv-7, results in specific T cell deletion in the absence of a detectable proliferative response. Finally, we show by secondary transfers of infected cells that exogenous MMTV(SW) is transmitted multidirectionally between lymphocyte subsets and ultimately to the mammary gland. Collectively our data demonstrate heterogeneity in the expression and/or presentation of endogenous and exogenous MMTV ORF by lymphocyte subsets and emphasize the low threshold required for induction of peripheral T cell deletion by these gene products.

Rearrangements in the long terminal repeat of extra mouse mammary tumor proviruses in T-cell leukemias of mouse strain GR result in a novel enhancer-like structure

1985 ◽  
Vol 5 (4) ◽  
pp. 823-830
Author(s):  
R Michalides ◽  
E Wagenaar ◽  
P Weijers
Keyword(s):  
T Cell ◽  
Mammary Tumor ◽  
Low Frequency ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Long Terminal Repeats ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Tandem Repeat Region

Male GR mice develop T-cell leukemia at low frequency late in life. These leukemia cells invariably contain large amounts of mouse mammary tumor virus (MMTV) RNA and MMTV proteins and have extra MMTV proviruses integrated in their DNA. We show here that the extra MMTV proviruses are all derived from the endogenous MMTV provirus associated with the Mtv-2 locus and that the T-cell leukemias are clonal with respect to the acquired MMTV proviruses. The extra MMTV proviruses in six transplantable T-cell leukemia lines studied had rearranged, shortened long terminal repeats (LTRs); each T-cell leukemia, however, had a different LTR rearrangement within its extra MMTV provirus. The alteration within the extra LTRs of T-cell leukemia line 42 involved deletion of 453 nucleotides and generation of a tandem repeat region consisting of regions flanking the deletion. This alteration generated a sequence similar to the adenovirus enhancer core sequence. The viral RNAs in the T-cell leukemias contained corresponding alterations in their U3 regions. These results demonstrate that expression of MMTV in T-cell leukemias of GR mice may be the consequence of the generation of a novel enhancer, which could also stimulate expression of any adjacent cellular oncogene.

scholarly journals Two classes of mutant mammary tumor virus-infected HTC cell with defects in glucocorticoid-regulated gene expression.

1983 ◽  
Vol 3 (2) ◽  
pp. 149-160 ◽  
Author(s):  
G L Firestone ◽  
K R Yamamoto
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Mammary Tumor ◽  
Hormonal Regulation ◽  
Wild Type ◽  
Viral Glycoprotein ◽  
Mammary Tumor Virus ◽  
Viral Glycoproteins ◽  
Tumor Virus ◽  
Regulated Gene Expression

We have isolated mutant derivatives of M1.54 (a mammary tumor virus [MTV]-infected rat hepatoma [HTC] cell line containing multiple integrated proviruses) that fail to express hormone-inducible cell surface viral glycoproteins. In wild-type M1.54, the synthetic glucocorticoid dexamethasone selectively stimulates the rate of synthesis of MTV RNA. In addition, dexamethasone is essential for posttranslational maturation of three of the four cell surface viral glycoproteins processed from the MTV glycosylated precursor polyprotein; the fourth mature species is produced constitutively. Two mutant phenotypes are described; each contains glucocorticoid receptors that are indistinguishable from the wild-type receptor with respect to hormone affinity, intracellular concentration, nuclear translocation efficiency, DNA-cellulose chromatography, and sedimentation rate. In one class, represented by the mutant line CR1, dexamethasone fails to stimulate the low basal rate of MTV gene transcription; surprisingly, hormonal regulation of tyrosine aminotransferase activity is also defective in CR1, whereas several other cellular responses to dexamethasone are normal. In the second class of mutants, represented by CR4, dexamethasone stimulates synthesis of MTV transcripts indistinguishable from those produced in M1.54, but only the constitutive cell surface viral glycoprotein is expressed. Thus, these mutants define two distinct and novel aspects of glucocorticoid regulated gene expression in HTC cells: CR4 contains a defect in a hormone inducible protein maturation pathway that acts on specific viral (and presumably cellular) precursor polypeptides, whereas the lesion in CR1 appears to affect the expression of a subset of the gene products normally under glucocorticoid control in M1.54.

scholarly journals Identification of Key Amino Acids of the Mouse Mammary Tumor Virus Superantigen Involved in the Specific Interaction with T-Cell Receptor Vβ Domains

2001 ◽  
Vol 75 (16) ◽  
pp. 7453-7461 ◽  
Author(s):  
Frédéric Baribaud ◽  
Susanne Wirth ◽  
Ivan Maillard ◽  
Sandrine Valsesia ◽  
Hans Acha-Orbea ◽  
...  
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
T Cell Receptor ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Specific Interaction ◽  
Cell Receptor ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Mouse mammary tumor virus (MMTV) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class II by the variable region of the beta chain (Vβ) of the T-cell receptor. The C-terminal 30 to 40 amino acids of the superantigen of different MMTVs display high sequence variability that correlates with the recognition of particular T-cell receptor Vβ chains. Interestingly, MMTV(SIM) andmtv-8 superantigens are highly homologous but have nonoverlapping T-cell receptor Vβ specificities. To determine the importance of these few differences for specific Vβ interaction, we studied superantigen responses in mice to chimeric and mutant MMTV(SIM) and mtv-8 superantigens expressed by recombinant vaccinia viruses. We show that only a few changes (two to six residues) within the C terminus are necessary to modify superantigen recognition by specific Vβs. Thus, the introduction of the MMTV(SIM) residues 314-315 into themtv-8 superantigen greatly decreased its Vβ12 reactivity without gain of MMTV(SIM)-specific function. The introduction of MMTV(SIM)-specific residues 289 to 295, however, induced a recognition pattern that was a mixture of MMTV(SIM)- and mtv-8-specific Vβ reactivities: both weak MMTV(SIM)-specific Vβ4 and fullmtv-8-specific Vβ11 recognition were observed while Vβ12 interaction was lost. The combination of the two MMTV(SIM)-specific regions in the mtv-8superantigen established normal MMTV(SIM)-specific Vβ4 reactivity and completely abolished mtv-8-specific Vβ5, -11, and -12 interactions. These new functional superantigens with mixed Vβ recognition patterns allowed us to precisely delineate sites relevant for molecular interactions between the SIM or mtv-8 superantigen and the T-cell receptor Vβ domain within the 30 C-terminal residues of the viral superantigen.

scholarly journals Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

2000 ◽  
Vol 74 (20) ◽  
pp. 9786-9791 ◽  
Author(s):  
Shin-ichi Yanagawa ◽  
Jong-Seo Lee ◽  
Kazuhiro Kakimi ◽  
Yukihiro Matsuda ◽  
Tasuku Honjo ◽  
...  
Keyword(s):  
T Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Insertional Mutagenesis ◽  
Wild Type Mouse ◽  
Long Terminal Repeats ◽  
Mammary Tumor Virus ◽  
T Cell Lymphomas ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT In contrast to wild-type mouse mammary tumor virus (MMTV), the MMTV mutants with specific deletions in the U3 region of their long terminal repeats cause T-cell lymphomas. In 30% of T-cell lymphomas arising in BALB/c mice infected with MLA-MMTV, a leukemogenic MMTV mutant, we have found that MMTV proviruses were integrated into a short region of theNotch1 genome, so that truncated Notch1transcripts encoding the transmembrane and the cytoplasmic domains of Notch1 protein could be expressed. Thus, Notch1 is a major target of provirus insertional mutagenesis in these T-cell lymphomas.

scholarly journals A Novel Block to Mouse Mammary Tumor Virus Infection of Lymphocytes in B10.BR Mice

2007 ◽  
Vol 82 (3) ◽  
pp. 1314-1322 ◽  
Author(s):  
Chioma M. Okeoma ◽  
Ming Shen ◽  
Susan R. Ross
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Cell Activation ◽  
Mouse Strains ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Mhc Locus

ABSTRACT Classic studies on C57BL-derived mouse strains showed that they were resistant to mouse mammary tumor virus (MMTV) infection. Although one form of resistance mapped to the major histocompatibility complex (MHC) locus, at least one other, unknown gene was implicated in this resistance. We show here that B10.BR mice, which are derived from C57BL mice but have the same MHC locus (H-2 k ) as susceptible C3H/HeN mice, are resistant to MMTV, and show a lack of virus spread in their lymphoid compartments but not their mammary epithelial cells. Although in vivo virus superantigen (Sag)-mediated activation of T cells was similar in C3H/HeN and B10.BR mice, T cell-dependent B-cell and dendritic cell activation was diminished in the latter. Ex vivo, B10.BR T cells showed a diminished capacity to proliferate in response to the MMTV Sag. The genetic segregation of the resistance phenotype indicated that it maps to a single allele. These data highlight the role of Sag-dependent T-cell responses in MMTV infection and point to a novel mechanism for the resistance of mice to retroviral infection that could lead to a better understanding of the interplay between hosts and pathogens.

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