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Molecular mechanism of allelic exclusion of TCR alpha chains
Author(s) -
Rybakin Vasily,
Gascoigne Nicholas R. J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.661.4
Subject(s) - allelic exclusion , locus (genetics) , allele , t cell receptor , alpha chain , biology , thymocyte , flow cytometry , microbiology and biotechnology , genetics , receptor , t cell , gene , immune system
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.