scholarly journals The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens.

1992 ◽  
Vol 175 (1) ◽  
pp. 41-47 ◽  
Author(s):  
A M Pullen ◽  
Y Choi ◽  
E Kushnir ◽  
J Kappler ◽  
P Marrack
Keyword(s):  
Mammary Tumor ◽  
Sequence Data ◽  
Cell Receptor ◽  
Open Reading Frames ◽  
Long Terminal Repeats ◽  
Tumor Viruses ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Terminal Repeats ◽  
Reading Frames

Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element.

scholarly journals Direct evidence for the role of COOH terminus of mouse mammary tumor virus superantigen in determining T cell receptor V beta specificity.

1993 ◽  
Vol 178 (2) ◽  
pp. 737-741 ◽  
Author(s):  
K Yazdanbakhsh ◽  
C G Park ◽  
G M Winslow ◽  
Y Choi
Keyword(s):  
T Cell ◽  
Mammary Tumor ◽  
Transmembrane Domain ◽  
Cell Receptor ◽  
Integral Membrane Protein ◽  
Lysine Residue ◽  
Open Reading Frames ◽  
Long Terminal Repeats ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

It has recently been shown that open reading frames in the 3' long terminal repeats of mouse mammary tumor viruses encode superantigens. These viral superantigens (vSAGs) stimulate most T cells expressing appropriate V beta s almost regardless of the rest of the variable components of the T cell receptors (TCR) expressed by those cells. vSAGs produce a type II integral membrane protein with a nonessential short cytoplasmic domain and a large glycosylated extracellular COOH-terminal domain, which is predicted to interact with major histocompatibility complex class II molecules and the TCR. The transmembrane region of vSAG also has an internal positively charged lysine residue of unknown significance. A set of chimeric and mutant vSAG genes has been used in transfection experiments to show that only the extreme COOH-terminal portion of vSAGs determine their TCR V beta specificities, and to show that the lysine residue in the transmembrane domain is not essential for the function of vSAG.

scholarly journals Mouse mammary tumor virus with rearranged long terminal repeats causes murine lymphomas.

1993 ◽  
Vol 67 (1) ◽  
pp. 112-118 ◽  
Author(s):  
S Yanagawa ◽  
K Kakimi ◽  
H Tanaka ◽  
A Murakami ◽  
Y Nakagawa ◽  
...  
Keyword(s):  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Long Terminal Repeats ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Terminal Repeats

Electron Immunochemical Labeling of Ultrathin Sections of Murine Tumor Viruses and Cell Cultures using the Unlabeled Antibody Enzyme Technique

1976 ◽  
Vol 34 ◽  
pp. 266-267
Author(s):  
W. J. Hamilton
Keyword(s):  
Mammary Tumor ◽  
Leukemia Virus ◽  
Parallel Methods ◽  
Tumor Viruses ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Antibody Conjugates ◽  
Rauscher Leukemia ◽  
Antigen Localization ◽  
Unlabeled Antibody

The study of RNA tumor viruses has been greatly facilitated by the use of immunochemical tagging methods. In the past these methods have been constrained to antibody conjugates with ferritin or peroxidase. In order to avoid the disadvantages of using conjugated antisera, investigators have applied the unlabeled antibody enzyme method of Sternberger to mammary tumor derived mouse cells prior to embedding for electron microscopy. The current study has successfully applied the Sternberger method to virusproducing cells and purified virus pellets after epoxy-embedding and ultrathin sectioning. The results demonstrate the distinct advantages of this “post-embedding” method for viral antigen localization.Purified Rauscher leukemia virus (RLV) and mouse mammary tumor virus (MMTV) were pelleted, fixed in buffered 2% paraformaldehyde and washed thoroughly. These were dehydrated in acetone, infiltrated and embedded in Spurr resin according to common procedures. A tumor derived cell line, Mm5mt, producing MMTV was embedded by parallel methods.

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 Structural analysis of a mouse mammary tumor virus superantigen.

1992 ◽  
Vol 175 (3) ◽  
pp. 847-852 ◽  
Author(s):  
Y Choi ◽  
P Marrack ◽  
J W Kappler
Keyword(s):  
Amino Acids ◽  
T Cells ◽  
Mammary Tumor ◽  
Integral Membrane Protein ◽  
Open Reading Frames ◽  
In Vitro Translation ◽  
Type Ii ◽  
Long Terminal Repeats ◽  
Mouse Mammary Tumor

It has recently been shown that the minor lymphocyte stimulating-like products expressed by some mice are actually encoded by open reading frames in the 3' long terminal repeats of mouse mammary tumor viruses. These products act as viral superantigens (vSAGs). That is, they stimulate most T cells bearing particular V beta s almost regardless of the rest of the variable components of the T cell receptors expressed by those cells. To find out more about the structure of these vSAGs, a set of truncated vSAG genes was used in transfection and in vitro translation experiments to show that the functional vSAG is a type II integral membrane protein with a large glycosylated extracellular COOH-terminal domain and a small, nonessential, intracellular NH2-terminal cytoplasmic domain. These results are consistent with the fact that the vSAGs must be expressed on the cell surface in order to interact with T cells and class II major histocompatibility complex proteins. They also account for the finding that much of the V beta specificity of the vSAGs is controlled by amino acids at the COOH-terminal end of the vSAG proteins, amino acids that will be extracellular in type II proteins.

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 The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire.

1995 ◽  
Vol 182 (5) ◽  
pp. 1493-1504 ◽  
Author(s):  
M T Scherer ◽  
L Ignatowicz ◽  
A Pullen ◽  
J Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mammary Tumor ◽  
T Cell Repertoire ◽  
Long Terminal Repeats ◽  
Cell Repertoire ◽  
Complex Molecules ◽  
Tumor Viruses ◽  
Individual Mouse ◽  
Tumor Virus

Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3' long terminal repeats of endogenous mammary tumor viruses (Mtv's). A line of Mtv-negative mice and several lines of mice containing single Mtv's were created by inbreeding the F2 progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2k mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the V beta repertoire, there are no super-antigens, other than those encoded by Mtv's, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv-negative mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection. vSAG3 was found to delete V beta 5 T cells, while vSAG8 deleted V beta 7 T cells, and vSAG9 deleted V beta 13 T cells in addition to their previously reported specificities. vSAG17 deletes a small proportion of CD4+ T cells bearing V beta 11 and -12. vSAG14 and -30 have little effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular V beta may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant V beta s. We found evidence that vSAG11 may positively select T cells bearing V beta 8.2. Our data, which analyzed the effects of seven endogenous Mtv's, showed little evidence of positive selection by any other vSAGs on T cells bearing any V beta tested, despite published reports to the contrary.

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