First Author | Wang F | Year | 1998 |
Journal | Proc Natl Acad Sci U S A | Volume | 95 |
Issue | 20 | Pages | 11834-9 |
PubMed ID | 9751751 | Mgi Jnum | J:50143 |
Mgi Id | MGI:1289958 | Doi | 10.1073/pnas.95.20.11834 |
Citation | Wang F, et al. (1998) Rapid deletion of rearranged T cell antigen receptor (TCR) Valpha-Jalpha segment by secondary rearrangement in the thymus: role of continuous rearrangement of TCR alpha chain gene and positive selection in the T cell repertoire formation. Proc Natl Acad Sci U S A 95(20):11834-9 |
abstractText | A rearranged T cell receptor (TCR) Valpha and Jalpha gene from a cytochrome c-specific T cell hybridoma was introduced into the genomic Jalpha region. The introduced TCR alpha chain gene is expressed in a majority of CD3 positive and CD4 CD8 double-negative immature thymocytes. How-ever, only a few percent of the double-positive and single-positive thymocytes express this TCR alpha chain. This decrease is caused by a rearrangement of TCR alpha chain locus, which deletes the introduced TCR gene. Analysis of the mice carrying the introduced TCR alpha chain and the trans-genic 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 alpha chain gene. In the mice with negatively selecting conditions, T cells expressing the introduced TCR alphabeta chains were deleted at the double-positive stage. However, a large number of thymocytes escape negative selection by using an endogenous TCR alpha chain created by secondary rearrange-ment maintaining normal thymocyte development. These results suggest that secondary rearrange-ments of the TCR alpha chain gene play an important role in the formation of the T cell repertoire. |