Sano T, Yamamoto K, Fukui Y, Sasazuki T
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Eur J Immunol. 1999 Feb;29(2):403-12. doi: 10.1002/(SICI)1521-4141(199902)29:02<403::AID-IMMU403>3.0.CO;2-1.
While much is known concerning CD4+ CD8+ thymocytes positively or negatively selected through interaction of their TCR with self peptides bound to self-MHC molecules, little is known of the majority of CD4+ CD8+ thymocytes lacking this interaction. We developed a monoclonal antibody (mAb) 1D11, the ligand of which (1D11-L) is expressed on 60-70% of CD4+ CD8+ thymocytes but not on other subsets of thymocytes and peripheral T cells. 1D11-L expression on CD4+ CD8+ thymocytes reversely correlates with their TCR engagement, in vitro and in vivo. In addition, 1D11-L+ CD4+ CD8+ thymocytes were more susceptible than 1D11-L- CD4+ CD8- thymocytes to apoptosis. We also found that T lineage cells other than CD4+ CD8+ thymocytes and a Thy-1-expressing fibroblast cell line became positive for 1D11-L by cross-linking their Thy-1 antigens with anti-Thy-1 mAb but not with their Fab fragment, suggesting that 1D11 recognizes multimerized Thy-1 antigens. Confocal laser scanning microscopy revealed that Thy-1 antigens as well as 1D11-L are clustered on some CD4+ CD8+ thymocytes but not on the other subsets of thymocytes. Taken together, we suggest that clustering of Thy-1 antigens spontaneously and specifically occurs on CD4+ CD8+ thymocytes lacking TCR engagement by MHC/peptide complexes.
虽然对于通过其TCR与结合于自身MHC分子的自身肽相互作用而被阳性或阴性选择的CD4+CD8+胸腺细胞，我们已经了解很多，但对于缺乏这种相互作用的大多数CD4+CD8+胸腺细胞却知之甚少。我们开发了一种单克隆抗体（mAb）1D11，其配体（1D11-L）在60%-70%的CD4+CD8+胸腺细胞上表达，但在胸腺细胞和外周T细胞的其他亚群上不表达。在体外和体内，CD4+CD8+胸腺细胞上1D11-L的表达与其TCR结合呈负相关。此外，1D11-L+CD4+CD8+胸腺细胞比1D11-L-CD4+CD8-胸腺细胞更容易发生凋亡。我们还发现，除CD4+CD8+胸腺细胞外的T谱系细胞和一种表达Thy-1的成纤维细胞系，通过用抗Thy-1 mAb交联其Thy-1抗原而不是用其Fab片段交联，会使1D11-L呈阳性，这表明1D11识别多聚化的Thy-1抗原。共聚焦激光扫描显微镜显示，Thy-1抗原以及1D11-L在一些CD4+CD8+胸腺细胞上聚集，但在胸腺细胞的其他亚群上不聚集。综上所述，我们认为Thy-1抗原的聚集在缺乏MHC/肽复合物TCR结合的CD4+CD8+胸腺细胞上自发且特异性地发生。
