Tcrb-V3+3T-cell deletion and a new mouse mammary tumor provirus,Mtv-44

Abstract

Genes encoding endogenous superantigens causing Tcrb-V3+ T-cell deletion co-segregate with mouse mammary tumor proviruses (Mtv), Mtv-3, Mtv-6, and Mtv-13. In addition Mtv-1 has been implicated in deletion of these T cells. We have examined levels of Tcrb-V3+ T cells and Mtv integrations in the following offspring and their parental strains, [(CBA-T6 x NZW)F1 x CBA], [(CBA x C3H/He)F1 x CBA], and [(B10.S (9R) x NOD]F1 mice. We show that a new Mtv (Mtv-44) from NZW mice and Mtv-1 from C3H/He mice cosegregate with genes encoding ligands for partial deletion of Tcrb-V3+ T cells and that some NOD mice have an additional Mtv (Mtv-45) which is closely linked to Mtv-3.

T‐Cell Receptor Repertoire Selection by Mouse Mammary Tumor Viruses and MHC Molecules

“…and see Tomonari et al, this volume) has been found to produce a deletion phenotype similar to Mtv-7 and -43, as does an exogenous MMTV transferred accidentally during embryo transfer to BALB/c stock (Held et al 1992). Interestingly, Mtv-44 also affects selection of T cells expressing V;ff3, previously found to be affected by several Mtv integrations (Fairchild et al 1991, Tomonari et al, 1992a, 1992c, Tomonari & Fairchild 1992, Pullen et al 1992). The identification of the Mtv-encoded product responsible for the Mis and TCR V^ deletion effects came from studies using transgenic mice and transfectants used to stimulate appropriate TCR V^-expressing hybridomas, Acha-Orbea et al (1991) found that not only mice transgenic for the entire GR-Mtv-2 genome, but also those transgenic for sequences limited to the open reading frame (ORF) within the LTR of this Mtv deleted V^14+ T cells.…”

“…Work of Frankel et al (1991) on inbred and recombinant inbred mice had shown that the Mls^ phenotype could be accounted for by the Mtv-7 integration on chromosome 1 in all but one of the strains examined, but that in the MA/J strain another Mtv integrant (subsequently identified as Mtv-43) ) was responsible. Since that time, a further integrant, Miv-44 (Fairchild et al 1992, 1992Blackman et al, 1992Woodland et al 1991Frankel et al I99f Rudy et al 1992Tomonari & Eairchild 1992Pullen etal. 19S8 Abeet al 1988P .. Frankel et al 1991Fairchild et al, 1992Tomonari et al 1992Woodland et al, 1990Gollob & Palmer 1992 Woodland et a!, 1991 (E) Dyson et al 1991Dyson et al 1991Marrack et al 1991Choi et al 1991Acha-Orbea et al 1991 * Deletion implied from T-cell stimulation by transfectants.…”

“…Since that time, a further integrant, Miv-44 (Fairchild et al 1992, 1992Blackman et al, 1992Woodland et al 1991Frankel et al I99f Rudy et al 1992Tomonari & Eairchild 1992Pullen etal. 19S8 Abeet al 1988P .. Frankel et al 1991Fairchild et al, 1992Tomonari et al 1992Woodland et al, 1990Gollob & Palmer 1992 Woodland et a!, 1991 (E) Dyson et al 1991Dyson et al 1991Marrack et al 1991Choi et al 1991Acha-Orbea et al 1991 * Deletion implied from T-cell stimulation by transfectants. and see Tomonari et al, this volume) has been found to produce a deletion phenotype similar to Mtv-7 and -43, as does an exogenous MMTV transferred accidentally during embryo transfer to BALB/c stock (Held et al 1992).…”

“…Tomonari MacDonald et al 1988 Benoist & Mathis 1989Tomonari & Fairchild 1992Tomonari et al 1992Tomonari et al 1992Liao et al 1989Blackman et al 1989Zuniga-Pflucker et al 1989Tomonari 1992 The feature shared by each of the observations derived from backcross analysis is that all mice inheriting the selecting MHC molecules show the same increased level of cells expressing the selected TCR V^ (Tomonari & Fairchild 1992, Tomonari et al 1992b, Tomonari 1992. This monophasic distribution is in contrast to the findings with negative selection, in which amongst mice sharing the same H-2 haplotype there is a bi-or tri-phasic distribution of the levels of cells expressing the selected TCR V^ , Tomonari & Fairchild 1991, Dyson et al 1991, Fairchild et al 1991, 1992, Fairchild & Tomonari 1992, Tomonari et al 1992a). The selection of V^6^ CD8^ T cells by various MHC class I alleles shows evidence of a hierarchy of affinity for this V/?…”

Mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models

“…Both the endogenous Mtv-3 and Mtv-17 proviral strains of MMTV have been identified in the NOD mouse and Mtv-8, Mtv-9, and Mtv-17 in the C57Bl genome [19,20]. Using PCR, both Mtv-3 and Mtv-17 were detected in the NOD.c3c4 genome (Fig.…”