Expression of a MHC class II transgene determines both superantigenicity and susceptibility to mammary tumor virus infection
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C Pucillo1, R Cepeda, R J Hodes
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
Milk-borne mouse mammary tumor virus (MMTV) is a type B retrovirus that induces mammary carcinoma. Infectious MMTV, as well as genomically integrated mouse mammary proviruses, encode superantigens that are recognized by T cells that express appropriate T cell receptor V beta products. To determine the relationship between the superantigenic property of milk-borne MMTV and its in vivo infectivity, mice which were either positive or negative for expression of a transgene-encoded E alpha E beta class II major histocompatibility complex (MHC) product were exposed to milk borne C3H MMTV. Superantigen-mediated deletion of V beta 14-expressing T cells occurred only in E alpha transgene-positive mice, indicating that the deletion was E alpha E beta dependent. When mice were analyzed for viral infection by assaying viral p28 in the milk of recipient females, significant p28 levels were found only in E alpha E beta transgene-positive mice. Similarly, the presence of C3H MMTV LTR mRNA in mammary glands, as detected by PCR, paralleled p28 levels. These findings indicate that E alpha expression or the E alpha-dependent T cell response to viral superantigen is causally related to susceptibility to MMTV infection, and that lack of a permissive class II product can protect mice from virus infection.
Insights
Mice exposed to milk-borne mouse mammary tumor virus (MMTV) showed infection susceptibility linked to their E alpha E beta major histocompatibility complex (MHC) expression. Lack of this MHC product protected mice from MMTV infection, highlighting its role in viral susceptibility.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Milk-borne mouse mammary tumor virus (MMTV) is a type B retrovirus causing mammary carcinoma.
- MMTV encodes superantigens recognized by T cells expressing specific T cell receptor V beta products.
- Superantigens play a role in T cell responses and immune system modulation.
Purpose of the Study:
- To investigate the relationship between MMTV superantigenicity and its infectivity in vivo.
- To determine the role of E alpha E beta class II major histocompatibility complex (MHC) expression in MMTV susceptibility.
- To understand how T cell responses to MMTV superantigens influence viral infection.
Main Methods:
- Mice with or without transgene-encoded E alpha E beta class II MHC product were exposed to milk-borne C3H MMTV.
- T cell deletion (V beta 14) was assessed to evaluate superantigen-mediated effects.
- Viral infection was quantified by measuring viral p28 in milk and MMTV LTR mRNA in mammary glands using PCR.
Main Results:
- Superantigen-mediated deletion of V beta 14 T cells occurred exclusively in E alpha E beta transgene-positive mice.
- Significant MMTV infection, indicated by p28 levels and LTR mRNA, was detected only in E alpha E beta transgene-positive mice.
- These results demonstrate a clear link between E alpha E beta expression and MMTV susceptibility.
Conclusions:
- E alpha expression or the E alpha-dependent T cell response to MMTV superantigen is causally related to MMTV infection susceptibility.
- The absence of a permissive class II MHC product confers protection against MMTV infection.
- This study elucidates a critical host genetic factor influencing retroviral infectivity and disease outcome.