Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission
W Held1, G A Waanders, A N Shakhov
1Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Abstract:
Endogenous and infectious mouse mammary tumor viruses (MMTVs) encode in their 3' long terminal repeat a protein that exerts superantigen activity; that is, it is able to interact with T cells via the variable domain of the T cell receptor (TCR) beta chain. We show here that transmission of an infectious MMTV is prevented when superantigen-reactive cells are absent through either clonal deletion due to the expression of an endogenous MTV with identical superantigen specificity or exclusion due to expression of a transgenic TCR beta chain that does not interact with the viral superantigen. A strict requirement for superantigen-reactive T cells is also seen for a local immune response following MMTV infection. This immune response locally amplifies the number of MMTV-infected B cells, most likely owing to their clonal expansion. Collectively, our data indicate that a superantigen-induced immune response is critical for the MMTV life cycle.
Insights
Mouse mammary tumor viruses (MMTVs) use a superantigen protein to interact with T cells. This interaction is essential for MMTV transmission and replication, highlighting the role of T cell responses in the viral life cycle.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Mouse mammary tumor viruses (MMTVs) are retroviruses known to cause mammary tumors in mice.
- MMTVs encode a superantigen protein within their 3' long terminal repeat (LTR).
- This viral superantigen interacts with the T cell receptor (TCR) beta chain, influencing immune responses.
Purpose of the Study:
- To investigate the role of T cell receptor (TCR) beta chain interactions in MMTV transmission and pathogenesis.
- To determine the necessity of superantigen-reactive T cells for MMTV infection and replication.
- To elucidate the mechanism by which MMTV utilizes the immune system for its life cycle.
Main Methods:
- Utilized genetically modified mice lacking superantigen-reactive T cells through clonal deletion or transgenic TCR beta chain expression.
- Assessed MMTV transmission and infectivity in these modified mouse models.
- Analyzed local immune responses and B cell proliferation following MMTV infection.
Main Results:
- Absence of superantigen-reactive T cells, via clonal deletion or transgenic TCR beta exclusion, prevented infectious MMTV transmission.
- Superantigen-reactive T cells are strictly required for a local immune response after MMTV infection.
- This immune response leads to the amplification of MMTV-infected B cells, likely through clonal expansion.
Conclusions:
- Superantigen-induced T cell responses are critical for the MMTV life cycle.
- MMTV transmission and replication are dependent on the interaction between the viral superantigen and specific T cells.
- Targeting these superantigen-TCR interactions could be a strategy to inhibit MMTV infection.
