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New infectious mammary tumor virus superantigen with V beta-specificity identical to staphylococcal enterotoxin B
S Luther1, A N Shakhov, I Xenarios
1Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Abstract:
Only few infectious mouse mammary tumor viruses (MMTV) have been characterized which induce a potent superantigen response in vivo. Here we describe the characterization of an MMTV which was isolated from milk of the highly mammary tumor-prone SHN mouse strain. Exposure of newborn mice to milk-borne MMTV (SHN) results in a very slow deletion of V beta 7, 8.1, 8.2 and 8.3 expressing peripheral T cells. Subcutaneous injection of adult mice with this virus induces a rapid and strong stimulation of all four affected V beta-subsets in vivo. Besides the strong T cell effect we observed an early proliferation and activation of the local B cell pool leading to the initial secretion of IgM followed by preferential secretion of IgG2a by day 6. Sequence comparison of the polymorphic C terminus with known open reading frames revealed high homology to the endogenous provirus Mtv-RCS. This is the first report of a virus having a complete overlap in V beta-specificity with a bacterial superantigen stimulating as many as 35% of the whole CD4+ T cell repertoire including V beta 8.2.
Insights
This study characterizes a novel mouse mammary tumor virus (MMTV) from SHN mice. The virus triggers a significant T cell response and B cell activation, impacting specific T cell subsets.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Few infectious mouse mammary tumor viruses (MMTVs) are known to induce potent in vivo superantigen responses.
- Mouse mammary tumor virus (MMTV) is associated with mammary tumors in mice.
Purpose of the Study:
- To characterize a newly isolated MMTV (MMTV-SHN) from the milk of the SHN mouse strain.
- To investigate the in vivo immune response induced by MMTV-SHN exposure in mice.
Main Methods:
- Isolation and characterization of MMTV from SHN mouse milk.
- Exposure of newborn and adult mice to MMTV-SHN.
- Analysis of T cell deletion (V beta subsets) and activation.
- Assessment of B cell proliferation and antibody secretion (IgM, IgG2a).
- Sequence analysis of the MMTV C terminus and comparison with known proviruses.
Main Results:
- MMTV-SHN exposure in newborn mice led to slow deletion of V beta 7, 8.1, 8.2, and 8.3 T cells.
- Subcutaneous injection in adult mice induced rapid and strong stimulation of these V beta subsets.
- Observed early B cell proliferation and activation, with IgM secretion followed by preferential IgG2a secretion.
- Sequence homology identified MMTV-SHN with the endogenous provirus Mtv-RCS.
- This MMTV demonstrated a complete overlap in V beta specificity with a bacterial superantigen, affecting up to 35% of CD4+ T cells.
Conclusions:
- MMTV-SHN is a potent inducer of T cell superantigen responses, affecting a significant portion of the CD4+ T cell repertoire.
- The virus also stimulates a robust local B cell response, indicating a complex interplay between MMTV and the host immune system.
- This characterization provides new insights into MMTV-driven immune modulation and its potential role in mammary tumorigenesis.