Syken Josh, Shatz Carla J
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13048-53. doi: 10.1073/pnas.1735415100. Epub 2003 Oct 20.
MHC class I proteins are cell-surface ligands that bind to T cell receptors and other immunoreceptors and act to regulate the activation state of immune cells. Recent work has shown that MHC class I genes and CD3zeta, an obligate component of T cell receptors, are expressed in neurons, are regulated by neuronal activity, and function in neuronal development and plasticity. A search for additional neuronally expressed T cell receptor components has revealed that the T cell antigen receptor beta (TCRbeta) locus is expressed in neurons of the murine central nervous system and that this expression is dynamically regulated over development. In neonates, expression is most abundant in various thalamic nuclei. At later ages and in adults, thalamic expression fades and cortical expression is robust, particularly in layer 6. In T cells, protein-encoding transcripts are produced only after recombination of the TCRbeta genomic locus, which joins variable, diversity, and joining regions, a process that creates much of the diversity of the immune system. We detect no genomic recombination in neurons. Rather, transcripts begin in regions upstream of several joining regions, and are spliced to constant region segments. One of the transcripts encodes a hypothetical 207-aa, 23-kDa protein, which includes the TCRbeta J2.7 region, and the entire C region. These observations suggest that TCRbeta may function in neurons.
MHC I类蛋白是细胞表面配体,可与T细胞受体及其他免疫受体结合,并调节免疫细胞的激活状态。最近的研究表明,MHC I类基因和CD3ζ(T细胞受体的一个必需成分)在神经元中表达,受神经元活动调控,并在神经元发育和可塑性中发挥作用。对其他神经元表达的T细胞受体成分的搜索发现,T细胞抗原受体β(TCRβ)基因座在小鼠中枢神经系统的神经元中表达,且这种表达在发育过程中受到动态调控。在新生儿中,各丘脑核中的表达最为丰富。在稍大年龄及成年时,丘脑表达减弱,而皮质表达活跃,尤其是在第6层。在T细胞中,只有在TCRβ基因组基因座发生重排后才会产生蛋白质编码转录本,该过程将可变区、多样区和连接区连接起来,这一过程造就了免疫系统的大部分多样性。我们在神经元中未检测到基因组重排。相反,转录本起始于几个连接区上游的区域,并剪接到恒定区片段。其中一个转录本编码一种假定的207个氨基酸、23 kDa的蛋白质,其包含TCRβ J2.7区和整个C区。这些观察结果表明TCRβ可能在神经元中发挥作用。