Beutner U, Rudy C, Huber B T
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
Int Rev Immunol. 1992;8(4):279-88. doi: 10.3109/08830189209053513.
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 V beta genes. 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 V beta specificity 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.
最近已经描述了一系列内源性和外源性超抗原，它们有一个共同特征，即它们导致表达特定T细胞受体Vβ基因的T细胞在体内缺失和体外刺激。Mls抗原是这些分子的原型。我们已将Mls-1定位到内源性乳腺肿瘤病毒（MMTV）Mtv-7，而其他超抗原也与各种MMTV相关。MMTV的开放阅读框基因编码超抗原。因此，已针对该基因提出了新术语MMTV sag。转染实验表明，MMTV sag的表达受到严格控制，可能是由开放阅读框内编码的负性作用因子控制。此外，在转染的Mtv-7 sag的功能检测中观察到明显的IL-4效应。由于这种淋巴因子不影响内源性或转染的MMTV基因的mRNA水平，它可能通过增加MHC II类基因的转录来发挥其作用，其产物是Mls功能检测所必需的。我们鉴定出一种小鼠品系MA/MyJ，它具有Mls-1表型但不包含Mtv-7。该品系的超抗原活性被定位到一种新的乳腺肿瘤前病毒Mtv-43，在其他近交系中未见。序列分析表明，Mtv-7和Mtv-43 sag基因的预测氨基酸序列非常相似。这在C末端尤为显著，所有其他MMTV sag序列在此处有100%的差异。因此，分子的这一区域似乎控制着超抗原分子的Vβ特异性。超抗原表达可能为感染性MMTV提供了优势，可能是通过促进其由T细胞从肠道的主要驻留部位传播到其最终目的地乳腺。
