Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

Beutner, Ulrich; Frankel, Wayne N.; Cote, Matthew S.; Coffin, John M.; Huber, Brigitte

doi:10.1073/pnas.89.12.5432

Cited by 73 publications

(66 citation statements)

References 31 publications

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“…ϩ DMB wild-type and mutant human B-LCL (18) were transfected with the Mtv-7 sag gene under control of the human ␤-actin promoter (15). Stable transfectants were screened for the level of DRB1*0301 expression by immunofluorescence, and matched clones were used for the functional stimulation of the V␤6 ϩ T cell hybrid, RG17 (19), at various responder to stimulator ratios.…”

Section: Drb1*0301mentioning

confidence: 99%

“…We show here that presentation of the Mtv-7 superantigen by class II, as measured by T cell recognition, does not require DM. The DRB1*0301-expressing DMB mutant (9.5.3) and wild-type (8.1.6) B lymphoblastoid cell lines (18) were transfected with Mtv-7 sag (15). Stable transfectants, matched for the level of DRB1*0301 on their cell surface and Mtv-7 sag mRNA (data not shown), were assayed for superantigen expression by their capacity to stimulate the V␤6 ϩ T cell hybrid, RG17 (19).…”

Section: Mmtv Superantigen Expression Does Not Require Dmmentioning

confidence: 99%

“…This same mutation was made in the wild-type Mtv-7 sag gene, referred to as P1S7, for the transfection experiments (see below), using the QuikChange site-directed mutagenesis kit (Stratagene, La Jolla, CA). The P1S7 construct was subcloned into ph␤APr-1-neo (15) to make ph␤A-P1S7. For the in vitro translation studies, the cDNAs of the Mtv-7 sag constructs were cloned into a mouse encephalomyocarditis virus promoter-driven expression vector (16).…”

Section: Constructs and Plasmidsmentioning

confidence: 99%

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Association of Mouse Mammary Tumor Virus Superantigen with MHC Class II During Biosynthesis

Hsu

Bryant

Sutkowski

et al. 2001

The Journal of Immunology

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Mouse mammary tumor viruses encode superantigens that interact with MHC class II proteins and stimulate T cells. We show here that presentation of mouse mammary tumor virus superantigen does not require DM. Furthermore, we have identified a strong class II peptide binding motif in the Mtv-7 superantigen, and we show that this motif is necessary for association with class II molecules in in vitro translation and in vivo functional assays. Our results suggest that endogenously synthesized viral superantigen can bind to MHC class II heterodimers during biosynthesis in the endoplasmic reticulum in a manner analogous to that used by the class II-associated invariant chain.

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Section: Drb1*0301mentioning

confidence: 99%

Section: Mmtv Superantigen Expression Does Not Require Dmmentioning

confidence: 99%

Section: Constructs and Plasmidsmentioning

confidence: 99%

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Association of Mouse Mammary Tumor Virus Superantigen with MHC Class II During Biosynthesis

Hsu

Bryant

Sutkowski

et al. 2001

The Journal of Immunology

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“…Mls-1 has been known to act as a minor lymphocyte-stimulating Ag. Subsequently, the Mls-1 Ag was shown to be encoded by the mtv-7 gene, which is a murine mammary tumor viral gene that has integrated into their genome of some strains of mice (34). These mice are referred to as Mls-1 a mice, while mice lacking this Ag are Mls-1 b .…”

Section: Figurementioning

confidence: 99%

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Ito

Takaishi

Jin

et al. 2000

The Journal of Immunology

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T cell responses to self Ags and normal microbial flora are carefully regulated to prevent autoreactivity. Because IL-10-deficient mice develop colitis, and this response is triggered by luminal flora, we investigated whether IL-10 regulates the ability of microbial Ags to induce autoreactive T cells that could contribute to intestinal inflammation. T cells from wild-type mice were primed with staphylococcal enterotoxin B (SEB) in vitro, which induced an autoreactive proliferative response to syngeneic feeder cells. The cells were predominately CD3+ and CD4+. T cells from IL-10-deficient mice were constitutively autoreactive, and SEB priming enhanced this further. The autoreactive, proliferative response of T cells from wild-type mice was suppressed by IL-10 in the primary or secondary culture, and this effect was inhibited by neutralizing Abs to the IL-10R. To confirm that an autoreactive repertoire was expanded after SEB priming, we used CBA/J mice (Mls-1a) in which autoreactive T cells recognizing the endogenous viral superantigen are depleted (Vβ6, 7, 8.1 TCR-bearing cells). However, SEB rescued these autoreactive T cell repertoires. Adding anti-MHC class II Ab blocked the autoreactive response. SEB-primed splenic or colonic T cells also induced apoptosis in syngeneic intestinal epithelial cells that was blocked significantly by IL-10. Thus, microbial Ags have the potential to abrogate self tolerance by stimulating autoreactive T cells that become cytolytic to target cells. IL-10 plays a protective role in maintaining self tolerance after microbial stimulation by preventing the activation of T cells that contribute to epithelial cell damage.

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“…The two strains of mice are identical at the MHC but differ in minor histocompatibility and in Mls antigens (Schirrmacher et al, 1995. The latter represent endogenous viral superantigens (vSAGs) which are encoded by mouse mammary tumour virus proviruses (Mtvs) that are integrated in murine genomes (Beutner et al, 1992). In contrast to conventional antigens, SAGs are presented by MHC II molecules outside the binding groove and are recognised by certain Vb-chains of the TCR (Choi et al, 1996).…”

mentioning

confidence: 99%

Superantigen reactive Vβ6+ T cells induce perforin/granzyme B mediated caspase-independent apoptosis in tumour cells

et al. 2002

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The endogenous viral superantigen 7 in DBA/2 mice serves as a target antigen on syngeneic ESb-MP lymphoma cells for allogeneic graft-vs-leukaemia reactive cells. Allogeneic viral superantigen 7 reactive Vb6 + T cells are able to transfer graft-vsleukaemia reactivity and to kill specifically viral superantigen 7 + ESb-MP tumour cells in vitro. Here we elucidate the mechanism of this superantigen specific cell lysis. Already 10 min after co-incubation with in vitro stimulated Vb6 + T cells, viral superantigen 7 + ESb-MP tumour cells show an apoptotic phenotype (Annexin V-positivity, DNA-fragmentation). This extremely rapid type of cell death is not mediated by the death inducing ligands CD95L, TRAIL and TNF but by perforin and granzyme B. Surprisingly, neither mitochondria nor any of the known caspases appear to be involved in this type of tumour cell killing. In contrast, nitric oxide, released by activated macrophages and endothelial cells, induces in the same tumour cells another type of apoptosis which is much slower and involves mitochondria and caspase activation. A synergistic effect between the two different effector mechanisms of superantigen reactive donor cytotoxic T lymphocytes and nitric oxide releasing host macrophages and endothelial cells might explain the effective immune rejection of even advanced metastasised cancer in this graft-vs-leukaemia animal model.

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Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

Cited by 73 publications

References 31 publications

Association of Mouse Mammary Tumor Virus Superantigen with MHC Class II During Biosynthesis

Association of Mouse Mammary Tumor Virus Superantigen with MHC Class II During Biosynthesis

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Superantigen reactive Vβ6+ T cells induce perforin/granzyme B mediated caspase-independent apoptosis in tumour cells

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