Naoya Niimi

A novel exogenous mammary tumor virus encoding MHC class II H2E-independent superantigen specific foor Tcr-Vβ14

Similar to the superantigens encoded by endogenous mouse mammary tumor virus (MMTV) proviruses (Acha-Orbea et al. 1993), infectious MMTVs express superantigens, which are recognized by particular Tcrb-V in the context of MHC class II molecules (Marrack et al. 1991). Choi and coworkers (1991) and Acha-Orbea and co-workers (1991) have reported independently that MMTV(C3H) and MMTV(GR) encode superantigens which interact with T cells expressing Tcr-V~314. Both retroviral superantigens require exclusively MHC class II H2E expression for presentation and clonal deletion, and do not induce vigorous T-cell proliferation (Held et al. 1992). We injected partially purified virus particles from the milk of RIII mice or II TES mice, which had been established by the crossbreeding of DBA/2 with strains of Japanese pet mouse origin (NBCS-II and CS), into the footpad of adult BALB/c or C57BL/6(B6), and the V~3 repertoire was examined in the popliteal LN cells 4 days after injection by flowcytometry. As shown in Figure 1, the V~314 T cells in CD4 + LN cells were increased in BALB/c mice 4 days after injection with the II-TES or RIII milk, while V[36 T cells were decreased in these mice, presum-

A new gene encoding the ligand for deletion of T cells bearing Tcrb-V6 and V8.1 (Mtv-50)

The minor lymphocyte-stimulating antigen (Mls), which is defined by the demonstration of a strong primary T-cell proliferative response in a mixed lymphocyte culture between major histocompatibility complex-identical strains, is a representative of self superantigens (Sags) which bind to certain Tcrb-V elements, and delete T cells bearing these elements. Mls-1 antigen encoded by Mtv-7 stimulates T cells bearing Tcrb-V6, V7, V8.1, or V9 in vitro, and delete these T cells in vivo. Recently, Mtv-43, Mtv-44, and exogenous MMTV (SW) have also been found to encode Mls-1-like antigens, which delete Tcrb-V6, V7 (except Mtv-44), V8.1- and/or V9-bearing T cells. In sharp contrast to Mls-1, Mls-1-like antigens encoded by Mtv-43 and MMTV(SW) show only a limited in vitro stimulatory capacity. 9 refs., 1 fig.

CD4 Expression is Important but not Essential for Infection with Exogenous Mouse Mammary Tumor Virus

We studied local events in the popliteal lymph nodes of CD4-deficient mice following foot pad injection with an MMTV strain which carries the gene for a V beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of CD4+/- heterozygous control mice. On the other hand, CD4-/- mice injected with the MMTV showed a proliferation of V beta 14+ T cells among the population of TCR alpha beta + CD4-CD8- T cells, although to a lesser extent. This phenomenon was not accompanied by vigorous B cell expansion. A PCR assay revelated that the MMTV definitely infected the lymph nodes cells of the CD4-/- mouse. However, the infectivity of the MMTV in CD4-/- mice was approximately 20 times lower than that in CD4+/- mice. These findings indicate that, in MMTV infection of CD4-deficient mice, the superantigen-reactive T cells among the population of TCR alpha beta +CD4-CD8- T cells substitute for the superantigen-reactive CD4- T cells of normal mice, and that the absence of CD4 molecules decreased the infectivity of MMTV because of insufficient expansion of the superantigen-reactive T cells.