Molecular mechanism of allelic exclusion of TCR alpha chains (84.2)

Abstract

Abstract Allelic exclusion is a mechanism whereby a product of single allele is selected for expression. In case of the T cell receptor, allelic exclusion takes place differently for TCRa and TCRb chains. For the TCRb chain, a successfully completed in-frame rearrangement of one locus effectively inhibits the rearrangement of the second locus. This inhibition is achieved as a result of signaling originated from a successfully formed dimer of the b chain with pre-Ta. In contrast, both TCRa alleles are rearranged, often multiple times, until the positive selection stage, when a single a chain in conjunction with a fixed b chain allows the thymocyte to differentiate. Majority of immature thymocytes express more than one a chain on the cell surface, while after positive selection only one chain is expressed. We developed and experimental system allowing to directly assess the fate of each of two specific a chains by flow cytometry and microscopy. Our studies are aimed at the better characterization of posttranslational modifications and signaling events leading to the selection of a single TCRa chain expressed at the cell surface.