Dyson P J, Elliott J I
Transplantation Biology Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, GB.
Eur J Immunol. 1999 May;29(5):1456-66. doi: 10.1002/(SICI)1521-4141(199905)29:05<1456::AID-IMMU1456>3.0.CO;2-D.
Though C57BL/10 mice express the mouse mammary tumor virus superantigens (sag) encoded by Mtv-8 and Mtv-9, it has been thought that these sag do not bind to the MHC class II molecule H2-Ab and consequently do not affect the T cell repertoire. However, we show that cells bearing TCR Vbeta chains specific for Mtv-8 and -9 sag are chronically deleted in C57BL/10 mice. Thymocytes and peripheral T cells escaping deletion by Mtv sag display a small reduction in the level of cell surface CD4. T cells escaping thymic deletion respond variably to endogenous Mtv sag with some, but not all, reactive populations appearing overrepresented in the activated/memory subset. The data suggest that in normal mice fine modulation of coreceptor expression levels may be a common way by which thymocytes escape elimination, that systems utilizing potentially Mtv sag-reactive TCR on a C57BL background may be inappropriate for the measurement of the affinity of TCR/MHC/peptide interactions required in thymic selection, and that detection of the activity of human sag may be aided by analysis of CD4 levels and activation markers on T cells in conjunction with studies of the frequency of cells bearing specific TCRVbeta chains.
尽管C57BL/10小鼠表达由Mtv-8和Mtv-9编码的小鼠乳腺肿瘤病毒超抗原(sag),但一直认为这些sag不与MHC II类分子H2-Ab结合,因此不影响T细胞库。然而,我们发现,在C57BL/10小鼠中,携带对Mtv-8和-9 sag特异的TCR Vβ链的细胞会被长期清除。逃避Mtv sag清除的胸腺细胞和外周T细胞在细胞表面CD4水平上有小幅降低。逃避胸腺清除的T细胞对内源性Mtv sag的反应各不相同,一些(但不是全部)反应性群体在活化/记忆亚群中似乎比例过高。数据表明,在正常小鼠中,共受体表达水平的精细调节可能是胸腺细胞逃避清除的常见方式,在C57BL背景下利用潜在的Mtv sag反应性TCR的系统可能不适用于测量胸腺选择中所需的TCR/MHC/肽相互作用的亲和力,并且通过分析T细胞上的CD4水平和活化标记,结合对携带特定TCRVβ链的细胞频率的研究,可能有助于检测人类sag的活性。