T-CELL RECEPTOR V-BETA REPERTOIRE IN MICE LACKING ENDOGENOUS MOUSE MAMMARY-TUMOR PROVIRUS

When endogenous mouse mammary tumor virus (MMTV) superantigens (SAg) are expressed in the first weeks of life an efficient thymic deletion of T cells expressing MMTV SAg-reactive T cell receptor (TcR) V beta segments is observed. As most inbred mouse strains and wild mice contain integrated MMTV DNA, knowing the precise extent of MMTV influence on T cell development is required in order to study T cell immunobiology in the mouse. In this report, backcross breeding between BALB.D2 (Mtv-6, -7, -8 and -9) and 38CH (Mtv(-)) mice was carried out to obtain animals either lacking endogenous MMTV or containing a single MMTV focus, i. e. Mtv-6, -7, -8 or -9. The TcR V beta chain (TcR V beta) usage in these mice was analyzed using monoclonal antibodies specific for TcR V beta 2, V beta 3, V beta 4, V beta 5, V beta 6, V beta 7, V beta 8, V beta 11, V beta 12 and V beta 14 segments. Both Mtv-8(+) mice and Mtv-9(+) mice deleted TcR V beta 5+ and V beta 11(+) T cells. Moreover, we also observed the deletion of TcR V beta 12(+) cells by Mtv-8 and Mtv-9 products. Mtv-6(+) and Mtv-7(+) animals deleted TcR V beta 3(+) and V beta 5(+) cells, and TcR V beta 6(+), V beta 7(+) and V beta 8.1(+) cells, respectively. Unexpectedly, TcR V beta 8.2(+) cells were also deleted in some backcross mice expressing Mtv-7. TcR V beta 8.2 reactivity to Mtv-7 was shown to be brought by the 38CH strain and to result from an amino acid substitution (Asn --> Asp) in position 19 on the TcR V beta 8.2 fragment. Reactivities of BALB.D2 TcR V beta 8.2 and 38CH TcR V beta 8.2 to the exogenous infectious viruses, MMTV(SW) and MMTV(SHN), were compared. Finally, the observation of increased frequencies of TcR V beta 2(+), V beta 4(+) and V beta 8(+) CD4(+) T cell subsets in Mrv-8(+) and Mtv-9(+) mice, and TcR V beta 4(+) CD4(+) T cells in Mtv-6(+) and Mtv-7(+) mice, when compared with the T cell repertoire of Mrv(-) mice, is consistent with the possibility that MMTV products contribute to positive selection of T cells.