Article: Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments.
Proceedings of the National Academy of Sciences of the United States of America
2000 Volume 97, Issue 14, Page(s) 7975–7980
Abstract: T cell receptor (TCR) beta variable region genes are assembled in progenitor T cells from germ-line Vbeta, Dbeta, and Jbeta segments via an ordered two-step process in which Dbeta to Jbeta rearrangements occur on both alleles before appendage of a Vbeta ... ...
Abstract | T cell receptor (TCR) beta variable region genes are assembled in progenitor T cells from germ-line Vbeta, Dbeta, and Jbeta segments via an ordered two-step process in which Dbeta to Jbeta rearrangements occur on both alleles before appendage of a Vbeta to a preexisting DJbeta complex. Direct joining of Vbeta segments to nonrearranged Dbeta or Jbeta segments, while compatible with known restrictions on the V(D)J recombination mechanism, are infrequent within the endogenous TCRbeta locus. We have analyzed mechanisms that mediate ordered Vbeta, Dbeta, and Jbeta assembly via an approach in which TCRbeta minilocus recombination substrates were introduced into embryonic stem cells and then analyzed for rearrangement in normal thymocytes by recombinase-activating gene 2-deficient blastocyst complementation. These analyses demonstrated that Vbeta segments are preferentially targeted for rearrangement to Dbeta as opposed to Jbeta segments. In addition, we further demonstrated that Vbeta segments can be appended to nonrearranged endogenous Dbeta segments in which we have eliminated the ability of Dbeta segments to join to Jbeta segments. Our findings are discussed in the context of the mechanisms that regulate the ordered assembly and utilization of V, D, and J segments. |
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MeSH term(s) | Animals ; Cell Lineage ; Chimera ; DNA-Binding Proteins/genetics ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Genes, T-Cell Receptor beta ; Genetic Complementation Test ; Mice ; Models, Genetic ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Recombination, Genetic |
Chemical Substances | DNA-Binding Proteins ; Rag2 protein, mouse ; Receptors, Antigen, T-Cell, alpha-beta ; V(D)J recombination activating protein 2 |
Language | English |
Publishing date | 2000-07-05 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. |
ZDB-ID | 209104-5 |
ISSN | 1091-6490 ; 0027-8424 |
ISSN (online) | 1091-6490 |
ISSN | 0027-8424 |
DOI | 10.1073/pnas.130190597 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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