A Vβ.2‐specific superantigen from exogenous mouse mammary tumor virus carried by FM mice

Abstract

A number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigen that have the ability to stimulate T cells with a certain T cell receptor (TCR) beta-chain variable region (V beta) and to mediate the V beta-specific clonal deletion. The tumorigenic milk-borne 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 MMTV 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 other known MMTV in the carboxy terminus implicated in TCR V beta recognition. Subcutaneous injection of the virus into adult BALB/c mice induced an approximately three- to fourfold enlargement of draining lymph nodes and a substantial increase of V beta 8.2+ CD4+ T cells in the lymph nodes within 6 days. The exposure of newborn BALB/c mice to the 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 demonstrated to be frequently involved in recognition of conventional antigens and responsible for autoimmune diseases such as experimental allergic encephalomyelitis. Therefore, the MMTV (FM) may provide a new mouse model system for inducing immunodeficiency or autoimmune disease by retroviral infection.

Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies

“…Branch lengths are indicative of the number of nucleotide changes to individual branch points (small numbers and see scale bar). The JYG (27), FM (28), and SW21 (29) (14,20,41,42) have also been associated with these two branches of the phylogenetic tree; however, no one patient has been reported to show association with more than one strain of MMTV.…”

“…All of the nucleotides were given equal weight; 391 were constant, 137 were parsimony-uninformative, and 140 were parsimony-informative. The JYG (27), FM (28), and SW21 (29) sequences from Asian mice were used to root the tree.…”

Critical Role of Dendritic Cells in Mouse Mammary Tumor Virus In Vivo Infection

“…MMTV(LA) and MMTV(FM) were isolated from milk, and MMTV(HP) was isolated from DC culture supernatants as previously described (18,19,43). Dilutions of purified virus were tested for B-cell-and Sag-mediated T-cell activation in vivo, as previously described (29).…”

RIII/Sa Mice with a High Incidence of Mammary Tumors Express Two Exogenous Strains and One Potential Endogenous Strain of Mouse Mammary Tumor Virus

“…The RIII/Sa MMTV-2 virus shares very close homology in the C terminus of the Sags of three other biologically different MMTV strains, FM, SHN, and Mtv-RCS (20,35,42) (Fig. 6).…”