A V-BETA-8.2 SPECIFIC SUPERANTIGEN FROM EXOGENOUS MOUSE MAMMARY-TUMORVIRUS CARRIED BY FM MICE

A number of endogenous mouse mammary tumor virus (MMTV) proviruses enc ode superantigen that have the ability to stimulate T cells with a cer tain T cell receptor (TCR) beta-chain variable region (V beta) and to mediate the V beta-specific clonal deletion. The tumorigenic milk-born e MMTV carried by C3H and GR mice also have superantigenic properties in vivo. In the present study we identified and characterized a novel V beta 8.2-specific superantigen of exogenous MMTV carried by FM mice. The open reading frame (ORF) in the 3' long terminal repeat of the MM TV was cloned by polymerase chain reaction with primers corresponding to conserved regions spanning the ORF coding region. Sequence analysis of the ORF revealed that there is no sequence identical to those in o ther known MMTV in the carboxy terminus implicated in TCR V beta recog nition. Subcutaneous injection of the virus into adult BALB/c mice ind uced an approximately three- to fourfold enlargement of draining lymph nodes and a substantial increase of V beta 8.2(+) CD4(+) T cells in t he lymph nodes within 6 days. The exposure of newborn BALB/c mice to t he virus by foster nursing resulted in a marked deletion of V beta 8.2 (+) cells both in CD4(+) and CD8(+) T cells. Thus, a novel milk-borne MMTV in FM mice expresses strong superantigenic properties capable of stimulating V beta 8.2(+) T cells. V beta 8.2(+) T cells have been dem onstrated to be frequently involved in recognition of conventional ant igens and responsible for autoimmune diseases such as experimental all ergic encephalomyelitis. Therefore, the MMTV (FM) may provide a new mo use model system for inducing immunodeficiency or autoimmune disease b y retroviral infection.