Engagement of the T-cell receptor during positive selection in the thymus down-regulates RAG-1 expression.
Publisher DOI
PubMed ID
1329099
Abstract
We have examined the expression of the recombination activating gene RAG-1 by in situ hybridization to thymi from mice bearing transgenes for the T-cell receptor (TCR) alpha chain, TCR beta chain, or both TCR alpha and beta chains. RAG-1 transcription was found in the thymic cortex of transgenic mice carrying a single TCR alpha- or TCR beta-chain transgene, comparable to normal mice. However, RAG-1 transcription was strikingly reduced in the thymic cortex from transgenic mice carrying both TCR alpha- and beta-chain genes and expressing major histocompatibility complex (MHC) class I (H-2b) molecules necessary for positive selection of the transgenic TCR. In contrast, thymi of transgenic mice also carrying both TCR alpha- and beta-chain genes but expressing MHC molecules (H-2d) that did not positively select the transgenic TCR displayed high levels of RAG-1 transcription. The low thymic RAG-1 expression coincided with high transgenic TCR alpha-chain surface expression and with inhibition of endogenous TCR alpha-chain rearrangement. Our findings suggest that binding of the TCR to self MHC molecules during positive selection down-regulates RAG-1 transcription in cortical thymocytes and thereby prevents further TCR alpha-chain rearrangements.
Date Issued
1992-10-15
Publication Type
Article
Language(s)
en
Author(s)
Brändle, D | |
Rülicke, T | |
Hengartner, H | |
Pircher, H |
Additional Credits
Journal
Proceedings of the National Academy of Sciences of the United States of America - PNAS
Publisher
National Academy of Sciences NAS
ISSN
0027-8424
Access(Rights)
restricted