标题:Rapid deletion of rearranged T cell antigen receptor (TCR) Vα-Jα segment by secondary rearrangement in the thymus: Role of continuous rearrangement of TCR α chain gene and positive selection in the T cell repertoire formation
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:1998
卷号:95
期号:20
页码:11834-11839
DOI:10.1073/pnas.95.20.11834
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:A rearranged T cell receptor (TCR) V and J gene from a cytochrome c-specific T cell hybridoma was introduced into the genomic J region. The introduced TCR chain gene is expressed in a majority of CD3 positive and CD4 CD8 double-negative immature thymocytes. However, only a few percent of the double-positive and single-positive thymocytes express this TCR chain. This decrease is caused by a rearrangement of TCR chain locus, which deletes the introduced TCR gene. Analysis of the mice carrying the introduced TCR chain and the transgenic TCR {beta} chain from the original cytochrome c-specific T cell hybridoma revealed that positive selection efficiently rescues double-positive thymocytes from the loss of the introduced TCR chain gene. In the mice with negatively selecting conditions, T cells expressing the introduced TCR {beta} chains were deleted at the double-positive stage. However, a large number of thymocytes escape negative selection by using an endogenous TCR chain created by secondary rearrangement maintaining normal thymocyte development. These results suggest that secondary rearrangements of the TCR chain gene play an important role in the formation of the T cell repertoire.