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Molecular characterization of Mls-1.
1Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
International Reviews of Immunology
|January 1, 1992
Summary
Mammary tumor viruses (MMTV) encode superantigens (SAG) that control T cell receptor V beta gene expression. These MMTV SAGs, like Mtv-7 and Mtv-43, are crucial for MMTV transmission and may influence T cell responses.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Superantigens (SAGs) are known to delete and stimulate T cells expressing specific T cell receptor V beta genes.
- Mammary tumor viruses (MMTV) are associated with various SAGs, with Mls antigens serving as prototypes.
- The MMTV open reading frame gene encodes SAGs, leading to the proposed terminology MMTV sag.
Purpose of the Study:
- To investigate the genetic basis and functional characteristics of MMTV-encoded superantigens.
- To identify novel MMTV proviruses associated with SAG activity.
- To elucidate the role of MMTV SAGs in T cell receptor specificity and viral transmission.
Main Methods:
- Mapping of Mls-1 to MMTV Mtv-7 and identification of Mtv-43 in a novel mouse strain.
- Transfection experiments to study MMTV sag expression control.
- IL-4 treatment to assess functional detection of MMTV sag and its effect on MHC class II gene transcription.
- Sequence analysis of Mtv-7 and Mtv-43 sag genes.
Main Results:
- MMTV sag expression is tightly regulated, potentially by a negative factor within the open reading frame.
- IL-4 enhances functional detection of Mtv-7 sag by increasing MHC class II gene transcription, not mRNA levels.
- A novel MMTV provirus, Mtv-43, was identified with Mls-1 phenotype in a mouse strain lacking Mtv-7.
- High sequence similarity between Mtv-7 and Mtv-43 sag genes, particularly at the C-terminus, suggests a role in V beta specificity.
Conclusions:
- MMTV SAGs play a critical role in shaping T cell responses by targeting specific T cell receptor V beta genes.
- The C-terminal region of MMTV SAGs is likely responsible for determining their V beta specificity.
- MMTV SAG expression may confer a transmission advantage to the infectious MMTV by facilitating T cell-mediated spread from the gut to mammary glands.