ISSN:0883-0185    

DOI:10.3109/08830189209053512

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Recently a series of endogenous and exogenous superantigens have been described which have one common feature, namely, they lead to in vivo deletion and in vitro stimulation of T cells expressing particular T cell receptor Vβgenes. The Mls antigens represent the prototypes of these molecules. We have mapped Mls-1 to the endogenous mammary tumor virus (MMTV) Mtv-7, while other SAG have also been associated with various MMTV. The open reading frame gene of the MMTV encodes the SAG. Thus, the new terminology MMTV sag has been proposed for this gene. Transfection experiments suggest that the expression of MMTV sag is tightly controlled, probably by a negative acting factor encoded within the open reading frame. Furthermore, a pronounced IL-4 effect is seen in the functional detection of the transfected Mtv-7 sag. Since this lymphokine does not influence the mRNA level of the endogenous or transfected MMTV genes, it is likely that it exerts its effect by increasing transcription of MHC class II genes, whose products are required for functional detection of Mls. We have identified one mouse strain, MA/MyJ, which has an Mls-1 phenotype but does not contain Mtv-7. The SAG activity of this strain was mapped to a new mammary tumor provirus, Mtv-43, not seen in other inbred strains. Sequence analyses revealed that the predicted amino acid sequences of the Mtv-7 and the Mtv-43 sag genes are very similar. This is particularly striking in the C-terminus, where all other MMTV sag sequences differ 100%. Thus, this region of the molecule seems to control the Vβspecificity of SAG molecules. It is likely that the SAG expression provides an advantage for the infectious MMTV, probably by facilitating its transmission by T cells from the site of primary residence in the gut to its final destination, the mammary glands.

ISSN:0883-0185    

DOI:10.3109/08830189209053513

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

It has recently become clear that the minor lymphocyte stimulatory antigens (Mls) and other endogenous ligands which lead to the partial or total deletion of T cells bearing particular Vβsegments are encoded by mouse mammary tumor virus (MMTV). We review here the genetic analyses of multiple Vβ11 and Vβ3 deletion ligands and demonstrate the involvement of MMTV in all examples. Several features of Mls and the Vβ11/Vβ3 deleting ligands identify them as members of the superantigen family. Bacterial superantigens are known to bind both MHC class II and the TCR in regions distinct from conventional peptide antigens. Within the MMTV genome, the 3’LTR has been identified as encoding superantigen function. We present data demonstrating that in vitro translation identifies the major product of the open reading frame (ORF) within the 3’LTR as a type II integral membrane glycoprotein. It is proposed that the type II membrane glycoprotein interacts with MHC and TCR in a manner analogous to the bacterial superantigens and distinct from conventional peptide antigen. Several unanswered questions regarding superantigen action remain; what determines total or partial deletion? How is Mls transferred between cells? These questions are addressed in the discussion.

ISSN:0883-0185    

DOI:10.3109/08830189209053514

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

For many years immunologists have been intrigued by a series of potent antigens encoded in the murine genome. These antigens, originally termed minor lymphocyte stimulating (Mls) antigens, are capable of inducing extremely strong T cell proliferative responses when presented in the context of MHC class II molecules. Recently, Mls antigens have been shown to stimulate T cells bearing particular T cell receptor Vβelements, leading to the designation of super-antigens. The endogenous expression of these super-antigens in mice results in the clonal elimination of large numbers of T cells in order to maintain self-tolerance. In this review we discuss the recent identification of endogenous super-antigens as retroviral gene products. In addition, we analyze the role of class II MHC molecules in the presentation of endogenous super-antigens to T cells. Finally, we discuss the dramatic effect of retroviral super-antigens on the T cell repertoire.

ISSN:0883-0185    

DOI:10.3109/08830189209053515

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The nature of the mysterious minor lymphocyte stimulating (Mls) antigens has recently been clarified. These molecules which were key elements for our current understanding of immune tolerance, have a strong influence on the mouse immune system and are encoded by the open reading frame (orf) of endogenous and exogenous mouse mammary tumor viruses (MMTV's). The knowledge that these antigens are encoded by cancerogenic retroviruses opens an interdisciplinary approach for understanding the mechanisms of immune responses and immune tolerance, retroviral carcinogenesis, and retroviral strategies for infection.

ISSN:0883-0185    

DOI:10.3109/08830189209053516

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

We have recently shown that expression vectors harboring the open reading frame of the long terminal repeat region of mouse mammary tumor virus direct the synthesis of a product which acts as a superantigen in transgenic mice. The detection of the ORF protein has been hampered by the extremely low levels of expression observed in these mice, as estimated from the low levels of specific mRNA. To study the properties of the ORF protein, we attempted its expression in different cell types in culture. The experiments performed in yeast show that the ORF gene product is a glycoprotein of approximately 45kDA. As expected from the derived primary sequence, the unglycosylated product made in the presence of tunicamycin has a molecular weight of 36kDA. No secretion of the glycosylated protein was observed. Curiously, the full-length molecule was made in lower amounts than a truncated version which contains only the C-terminal half of the protein. Transfection experiments in different mammalian cells suggest that high expression of the ORF protein might have an adverse effect on survival of cells in culture.

ISSN:0883-0185    

DOI:10.3109/08830189209053517

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor