Sant'Angelo D B, Cresswell P, Janeway C A, Denzin L K
Immunology Program, Memorial Sloan-Kettering Cancer Center, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA. d-sant'
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6824-9. doi: 10.1073/pnas.121179998. Epub 2001 May 29.
T cell receptor (TCR) allelic exclusion is believed to be primarily mediated by suppression of further recombination at the TCR locus after the expression of a functional TCR protein. Genetic allelic exclusion has been shown to be leaky for the beta chain and, more commonly, for the alpha chain. Here, we demonstrate an additional mechanism by which T cells can maintain monoclonality. T cells from double TCR transgenic mice express only one or the other of the two available TCRs at the cell surface. This "functional allelic exclusion" is apparently due to control of the TCR assembly process because these T cells express RNA and protein for all four transgenic TCR proteins. Lack of cell surface expression of the second TCR may be controlled by a failure to assemble the TCR heterodimer.
T细胞受体(TCR)等位基因排斥被认为主要是由功能性TCR蛋白表达后TCR基因座处进一步重组的抑制所介导。基因等位基因排斥已被证明对于β链而言是不完全的,而对于α链则更为常见。在此,我们展示了T细胞维持单克隆性的另一种机制。来自双TCR转基因小鼠的T细胞在细胞表面仅表达两种可用TCR中的一种或另一种。这种“功能性等位基因排斥”显然是由于TCR组装过程的控制,因为这些T细胞表达所有四种转基因TCR蛋白的RNA和蛋白质。第二种TCR缺乏细胞表面表达可能是由TCR异二聚体组装失败所控制。