文章基本信息

标题：Revision of T cell receptor α chain genes is required for normal T lymphocyte development
本地全文：下载
作者：Ching-Yu Huang ; Barry P. Sleckman ; Osami Kanagawa 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：40
页码：14356-14361
DOI：10.1073/pnas.0505564102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：To become mature {alpha}{beta} T cells, developing thymocytes must first assemble a T cell receptor (TCR) {beta} chain gene encoding a TCR{beta} chain that forms a pre-TCR. These cells then need to generate a TCR{alpha} chain gene encoding a TCR{alpha} chain, which, when paired with the TCR{beta} chain, forms a selectable {alpha}{beta} TCR. Newly generated VJ{alpha} rearrangements that do not encode TCR{alpha} chains capable of forming selectable {alpha}{beta} TCRs can be excised from the chromosome and replaced with new VJ{alpha} rearrangements. Such replacement occurs through the process of TCR{alpha} chain gene revision whereby a V{alpha} gene segment upstream of the VJ{alpha} rearrangement is appended to a downstream J{alpha} gene segment. A multistep, gene-targeting approach was used to generate a modified TCR{alpha} locus (TCR{alpha}sJ) with a limited capacity to undergo revision of TCR{alpha} chain genes. Thymocytes from mice homozygous for the TCR{alpha}sJ allele are defective in their ability to generate an {alpha}{beta} TCR. Furthermore, those thymocytes that do generate an {alpha}{beta} TCR have a diminished capacity to be positively selected, and TCR{alpha}sJ/sJ mice have significantly reduced numbers of mature {alpha}{beta} T cells. Together, these findings demonstrate that normal T cell development relies on the ability of developing thymocytes to revise their TCR{alpha} chain genes.
关键词：V(D)J recombination ; gene rearrangement ; T cell repertoire ; αβ T cell