Scherer M T, Ignatowicz L, Pullen A, Kappler J, Marrack P
Howard Hughes Medical Institute, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
J Exp Med. 1995 Nov 1;182(5):1493-504. doi: 10.1084/jem.182.5.1493.
Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3' long terminal repeats of endogenous mammary tumor viruses (Mtv's). A line of Mtv-negative mice and several lines of mice containing single Mtv's were created by inbreeding the F2 progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2k mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the V beta repertoire, there are no super-antigens, other than those encoded by Mtv's, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv-negative mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection. vSAG3 was found to delete V beta 5 T cells, while vSAG8 deleted V beta 7 T cells, and vSAG9 deleted V beta 13 T cells in addition to their previously reported specificities. vSAG17 deletes a small proportion of CD4+ T cells bearing V beta 11 and -12. vSAG14 and -30 have little effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular V beta may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant V beta s. We found evidence that vSAG11 may positively select T cells bearing V beta 8.2. Our data, which analyzed the effects of seven endogenous Mtv's, showed little evidence of positive selection by any other vSAGs on T cells bearing any V beta tested, despite published reports to the contrary.
大多数实验室小鼠品系有2至8种内源性超抗原。这些病毒超抗原（vSAGs）由内源性乳腺肿瘤病毒（Mtv's）3'长末端重复序列中的基因编码。通过对CBA/CaJ和C58/J小鼠的F2后代进行近亲繁殖，培育出了一个Mtv阴性小鼠品系和几个含有单个Mtv的小鼠品系，这两个亲本小鼠没有共同的Mtv整合体。这使得能够研究不受Mtv超抗原影响的H-2k小鼠的T细胞库，以及vSAGs对该库的影响。尽管每只小鼠都有不同的C58/J和CBA/CaJ背景基因组合，但不同的Mtv阴性小鼠的T细胞库非常相似且具有可重复性。由于背景基因不影响Vβ库，除了Mtv编码的超抗原外，CBA/CaJ和C58/J之间没有其他不同的超抗原。由于I类和II类主要组织相容性复合体分子对阳性和阴性选择的影响，Mtv阴性小鼠中的CD4和CD8 T细胞具有相当不同的库。除了先前报道的特异性外，还发现vSAG3可删除Vβ5 T细胞，vSAG8删除Vβ7 T细胞，vSAG9删除Vβ13 T细胞。vSAG17删除一小部分携带Vβ11和-12的CD4+ T细胞。vSAG14和-30对T细胞库影响很小，且不在胸腺细胞和脾细胞中表达。对特定Vβ亲和力低的内源性超抗原可能会阳性选择胸腺细胞，导致外周携带相关Vβ的T细胞频率增加。我们发现有证据表明vSAG11可能会阳性选择携带Vβ8.2的T细胞。我们分析了七种内源性Mtv影响的数据显示，尽管有相反的已发表报道，但几乎没有证据表明任何其他vSAGs对携带任何测试Vβ的T细胞有阳性选择作用。
