Disease relevance of Mtv13

• Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome [1].
• Bacterial toxins constitute the major group of exogenous SAGs, while the mouse mammary tumor virus (MMTV)-encoded Mls molecules represent the endogenous SAGs [2].
• The majority of endogenous superantigens in the mouse (including the Mls loci) is encoded by mouse mammary tumor proviruses (Mtv) carried in the germline [3].
• The responses of normal spleen cells to B cell lines that express the defective virus indicated that these lines express a cell surface determinant that shares "superantigenic" properties with some microbial antigens and Mls-like self antigens [4].
• The Mls gene products, which have long been known for their potent T-cell stimulatory function, have recently come of age through two pivotal discoveries, revealing that they act as superantigens and originate from retroviruses [5].

High impact information on Mtv13

• We report here the Mls 2a/3a mediated elimination of T cells expressing a transgene encoded V beta 3-segment, in T-cell receptor alpha/beta and beta-transgenic mice [6].
• Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex [7].
• Immunology. Tolerance, restriction and the Mls enigma [8].
• The only other potent primary proliferative response known is induced by mixing MHC-identical lymphocytes from strains that differ at the locus termed Mls (ref. 1) (for mixed lymphocyte stimulating), which has been mapped to chromosome 1 [9].
• It has been proposed that the Mls locus product is a minor antigen recognized in association with self-Ia antigens, a translocated Ia-like element, or a mitogenic molecule found on the surface of antigen presenting cells (APC) [9].

Chemical compound and disease context of Mtv13

• Benzanthracene-induced C57BL/6 (H-2b) mouse T-cell lymphoma EL4 (a thymidine kinase-deficient cell line) was fused by using polyethylene glycol with an Mlsa (Mls for minor lymphocyte stimulatory) antigen-dependent T cell line, which was designated G4 and had been derived from a C3H/He mouse (H-2k), and the fused cells were cultured in HAT medium [10].

Biological context of Mtv13

• It stimulates V beta 3+ hybrids and may be linked to Mtv-13 on chromosome 4 [11].
• Proliferative responses to M locus (Mls) determinants were investigated in vivo by injecting T cell-containing populations intravenously into irradiated H2-identical, Mls-incompatible mice [12].
• These findings suggest a new concept of the polymorphism and genetics of the Mls system [13].
• The peripheral level of V beta 3 transcripts vary with MHC and Mls-2 haplotypes [14].
• Thymic epithelium induces neither clonal deletion nor anergy to Mls 1a antigens [15].

Anatomical context of Mtv13

• Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes [11].
• Studies on non-H-2-linked lymphocyte-activating determinants. IV. Ontogeny of the Mls product on murine B cells [16].
• Proliferation of C3H x CBA hybrid lymphocytes in the spleens of irradiated CBA mice: linkage to the Mls-gene [17].
• Relative V beta transcript levels in thymus and peripheral lymphoid tissues from various mouse strains. Inverse correlation of I-E and Mls expression with relative abundance of several V beta transcripts in peripheral lymphoid tissues [14].
• Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells [18].

Associations of Mtv13 with chemical compounds

• Intrathymic clonal deletion of V beta 6+ T cells in cyclophosphamide-induced tolerance to H-2-compatible, Mls-disparate antigens [19].
• A qualitative difference was observed when analyses of inositol phosphate production were performed under optimal conditions of stimulation of the highly responsive T cell hybridoma (FJ8.1): only stimulation with CD3-specific mAb, but not Mls-expressing cells, could induce detectable inositol phosphate production [20].
• Our studies indicate that the A alpha and E alpha chains can present Mls gene products for the clonal deletion of V beta 6-bearing T cells, and that the A alpha q chain is defective in this process [21].

Other interactions of Mtv13

• Mls-1 and Mls-2 superantigens do not control susceptibility to collagen-induced arthritis in HI and HII mice [22].

Analytical, diagnostic and therapeutic context of Mtv13

• Since congenic resistant strains were not used, the possibility that the stimulation observed was in fact due to minor transplantation antigens rather than Mls determinants could not be excluded [12].
• We subsequently presented evidence which indicated that the mixed leukocyte reaction stimulatory products of DBA/2 and CBA/J were controlled by two independently segregating Mls loci [23].
• METHODS: C3H (H2k, Thy 1.2, Mls 2a) recipients were conditioned with 9.5 gray (Gy) of total body irradiation [24].
• The role of hemopoietic stem cells and other cell types in the induction and maintenance of immunologic tolerance in the thymus was investigated by intravenous injection of Mls-semi-allogeneic cells into newborn mice less than 24 hr after birth [25].
• The evolution of Vbeta6-expressing C3H (H2k, Thy 1.2, Mls a-) lymphocytes was investigated in C3H recipients mice pretreated with total body irradiation (TBI) or total lymphoid irradiation (TLI) and infusion of AKR (H2k, Thy 1.1, Mls a+) cells [26].

References