Analysis of Mlsc genetics. A novel instance of genetic redundancy.

Ryo, Akihide; Foo-Phillips, M; Hodes, Richard J.

doi:10.1084/jem.170.4.1059

Cited by 20 publications

(5 citation statements)

References 32 publications

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“…2; and reference 15). It has previously been reported that, unlike C3H/HeJ and DBA/2, CBA/J carries only one VB3-specific superantigen (31)(32)(33). The expression of this superantigen correlates with the presence of Mtv-6 (Table 1 and Fig.…”

Section: Resultsmentioning

confidence: 68%

The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens.

Pullen

Choi

Kushnir

et al. 1992

The Journal of Experimental Medicine

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SummaryMice expressing the minor lymphocyte stimulation antigens, Mls-1 a, -2 a, or -3 ~, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V~3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor VB element.A number of murine aUoantigens have been described that, in combination with MHC class II products, stimulate T cells bearing particular V3 elements (1-8). These alloantigens have been termed superantigens (9). Mice expressing such superantigens delete thymocytes bearing reactive V3 elements during development in the thymus (10). This clonal elimination of thymocytes maintains self-tolerance by preventing mature self-reactive T cells from reaching the periphery.The analysis of peripheral expression ofT cells bearing particular V3 elements has recently facilitated the mapping of several of these superantigens to particular chromosomal locations. Woodland et al. (11,12) found no recombinants between the gene encoding a superantigen (Etc-1), which causes deletion of V/~11-and VB5.2-bearing T cells, and a mouse mammary tumor virus (MTV) 1 integrant (Mtv-9) on chromosome 12. In addition, the genes for several other endogenous mouse superantigens map to the same chromosomal regions as MTV integrants (4,13,14). In the past, however, some recombinants between the genetic locations of mouse endogenous superantigens and Mtvs had been reported in the AKXD and BXD recombinant inbred mice. Suspecting that these reported recombinants may have been mistyped, Frankel et al. (15) found perfect correlation between the expression of several superantigens and presence of particular MTV integrants in these mice. Thus, these investigators suggested that MTV integrants themselves code for the endogenous mouse superantigens. Independently, Dyson et al. (16) arrived at the same conclusion after mapping several ligands that delete Vf111 + T cells.Recently, we have shown that the infectious milk-borne MTV carried by C3H/HeJ mice codes for a superantigen that interacts with T cells bearing 18). Furthermore, transfection experiments have shown that it is the product of the open reading frame (ORF) within the 3' long terminal repeat (LTR) of the C3H MTV that confers the ability to interact with TCK in a V~-specific manner (18). have shown, using a transgenic model, that the OKF of the infectious MTV transmitted in the milk of GR mice also causes deletion of Vf114 § thymocytes. We have suggested the name viral superantigen (vSAG) for these ORF genes.In this study, we have used mice expressing Mls-1 a -2 a, or -3 a singly on the B10.BR background to demonstrate conclusively the correlation between the expression of these Mls phenotypes and the presence of , respectively. Transfection exp...

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Section: Resultsmentioning

confidence: 68%

The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens.

Pullen

Choi

Kushnir

et al. 1992

The Journal of Experimental Medicine

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“…B10.BROBR animals are homozygous for the C57BR-derived, Va8-, V/3 locus. CBA/J animals express Mls-la and Mls-2a, and/or Mls-3 a ; these superantigens are dominant in Fts, and will cause the deletion of most T cells bearing V03, -6, -7, and -8 .1 (24,32,33,35,36). Among the backcrossed animals, we therefore expected that about half the animals would be homozygous for the V08 deletion, and about half would be heterozygous for Mlsla or its associated superantigen expression, and therefore delete V(07 (and V06)bearing cells.…”

Section: Resultsmentioning

confidence: 99%

The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells.

Marrack

Blackman

Kushnir

et al. 1990

The Journal of Experimental Medicine

325

201

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Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell-stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.

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“…Thus, it is conceivable that the Mls ¢ antigen which deletes Tcrb-V3 ÷ T cells (Pullen et al 1988;Fry and Marls 1988) and is expressed in BXD RI strains at various levels due to segregation of two different genes each encoding the antigen independently (Pullen et al 1989;Abe et al 1989) is indirectly involved in the variation of Tcrb-V4+CD8 + T cells from H-2 d Mls a+ BXD RI strains. Environmental influence on the level of Tcrb-V4 ÷ T cells cannot be excluded, although each set of RI strains examined here was housed in the same room.…”

Section: Al 1989) Appears To Cause Compensatory Increases Of Tcrb-v4mentioning

confidence: 99%