Disease relevance of Mtv9

• We have previously shown that mice expressing the Etc-1 superantigen, encoded by an open reading frame within the 3' long terminal repeat of the endogenous mouse mammary tumor provirus (Mtv), Mtv-9, delete T cells expressing either V beta 5 or V beta 11 gene segments [1].
• It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9 [2].

High impact information on Mtv9

• We also demonstrate that Mtv-9 transcripts are present in B cells expressing Etc-1 and suggest that the coligand recognized by roughly 15% of all T lymphocytes is encoded by the Mtv-9 genome [3].
• The gene encoding one of these cotolerogens maps to chromosome 12 and is linked to the endogenous provirus Mtv-9 [4].
• Cells expressing these mutated class II molecules efficiently presented two retroviral SAGs (Mtv-9 and Mtv-7) to T cells while they were unable to present the bacterial SAGs [5].
• To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene [2].
• We show that Mtv-8 controls a superantigen with similar specificity, and that both Mtv-8 and Mtv-9 stimulate some V beta 17+ T cells [6].

Biological context of Mtv9

• The deletion of I-E-reactive V beta 5.2-bearing T cells is dependent on the coexpression of an I-E tolerogenic coligand (Etc)14 and the gene for one of these coligands, Etc-1, maps to chromosome 12, near the mouse mammary tumour viral integrant, Mtv-9 [3].
• Here we report a perfect genetic linkage between Etc-1 and Mtv-9 and show that Etc-1 is also involved in the I-E-dependent deletion of T cells bearing V beta 5.1 and V beta 11 domains [3].
• We show here that the expression of one endogenous superantigen, Etc-1, is controlled by the expression of the open reading frame region of the 3' long terminal repeat of the mouse mammary tumor proviral gene, Mtv-9 [6].
• The third provirus was endogenous Mtv-9 and was located less than 500 base pairs from the 3' end of L1 [7].
• The potential of the full-length Mtv-8 and Mtv-9 proviruses to be transcribed, as indicated by their methylation status, was not dramatically different between differentiated and undifferentiated mammary cells in culture [8].

Anatomical context of Mtv9

• Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9 [9].
• The specific hypomethylation of a HpaII site in Mtv-9 is associated with expression of a 1.6 kb transcript in the lactating mammary gland [10].

Other interactions of Mtv9

• Both Mtv-8+ mice and Mtv-9+ mice deleted TcR V beta 5+ and V beta 11+ T cells [11].
• Yet, a slightly reduced level of V beta 5+ T cells is observed in HII animals which might correlate with the presence of Mtv-6 and Mtv-9 proviruses [12].
• DNAs comprising the entire Mtv-8 locus and the 3' portions of Mtv-9 and Mtv-17 were cloned [13].

Analytical, diagnostic and therapeutic context of Mtv9

• Expression of Ek alpha did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2q/q and H-2b/q progeny of (B10.Ek alpha x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA [14].
• This unit, termed unit XI and encoded by the genetic locus Mtv-17, has not been previously recognized in C57BL/6 DNA, but it can be clearly distinguished from the proviral units at Mtv-8 and Mtv-9 by Southern blot analysis under appropriate conditions [13].
• Restriction mapping indicated that the SC34 cDNA clone was a product of the Mtv-9 locus [15].
• Sequence analysis demonstrates that the U3 region of the expressed Mtv-9 long terminal repeat contains neither deletions nor insertions, and the well-characterized enhancer and promoter sites in the glucocorticoid response element which are known to be involved in transcriptional regulation of MMTV in mammary tissues have not been disrupted [9].

References