T cell receptor Vβ repertoire in mice lacking endogenous mouse mammary tumor provirus

Abstract 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) Vβ 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 locus, i.e. Mtv‐6, −7, −8 or − 9 . The TcR Vβ chain (TcR Vβ) usage in these mice was analyzed using monoclonal antibodies specific for TcR Vβ2,Vβ3, Vβ4,β5,Vβ6,Vβ7,Vβ8,Vβ11,Vβ12 and Vβ14 segments. Both Mtv‐8 + mice and Mtv‐9 + mice deleted TcR Vβ5 + and Vβ11 + T cells. Moreover, we also observed the deletion of TcR Vβ12 + cells by Mtv‐8 and Mtv‐9 products. Mtv‐6 + and Mtv‐7 + animals deleted TcR Vβ3 + and Vβ35 + cells, and TcR Vβ6 + ,Vβ7 + and Vβ8.1 + cells, respectively. Unexpectedly, TcR Vβ8.2 + cells were also deleted in some backcross mice expressing Mtv‐7 . TcR Vβ8.2 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 Vβ8.2 fragment. Reactivities of BALB.D2 TcR Vβ8.2 and 38CH TcR Vβ8.2 to the exogenous infectious viruses, MMTV(SW) and MMTV(SHN), were compared. Finally, the observation of increased frequencies of TcR Vβ2 + , Vβ4 + and Vβ8 + CD4 + T cell subsets in Mtv‐8 + and Mtv‐9 + mice, and TcR Vβ4 + CD4 + T cells in Mtv‐6 + and Mtv‐7 + mice, when compared with the T cell repertoire of Mtv − mice, is consistent with the possibility that MMTV products contribute to positive selection of T cells.