Mechanisms that direct ordered assembly of T cell receptor β locus V, D, and J gene segments Academic Article uri icon

Overview

MeSH Major

  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor beta
  • Receptors, Antigen, T-Cell, alpha-beta

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.

publication date

  • July 5, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC16655

Digital Object Identifier (DOI)

  • 10.1073/pnas.130190597

PubMed ID

  • 10869424

Additional Document Info

start page

  • 7975

end page

  • 80

volume

  • 97

number

  • 14