The role of superantigens in the immunobiology of retroviruses.

Murine mammary tumour viruses (MMTVs) are retroviruses that encode superantigens capable of stimulating T cells via superantigen-reactive T cell receptor V beta chains. MMTVs are transmitted to the suckling offspring via the milk. We have established that class II and B cell-deficient mice that were foster nursed by virus-secreting mice do not transfer infectious MMTVs to their offspring. No MMTV proviruses could be detected in the spleen and mammary tissue of these mice and there was no deletion of MMTV superantigen-reactive T cells. These results confirm that superantigen expression in the context of MHC class II molecules is required for MMTV transmission. We conclude that B cells are essential for the completion of the viral life cycle in vivo. This indicates that B cells are infected first and that viral amplification takes place only if infected B cells present the MMTV superantigen on their surface which, in turn, results in activation of T cells expressing the appropriate T cell receptor V beta chains. These activated T cells stimulate B cells which enables viral replication. Human T cells carry all the structural features required for an efficient response to murine retrovirally encoded superantigens. Superantigen-like stimulation of human T cells has been demonstrated in both infectious and autoimmune diseases. Human immunodeficiency virus may encode a superantigen but this has not been proven.