Mechanics of T cell receptor gene rearrangement

Curr Opin Immunol. 2009 Apr;21(2):133-9. doi: 10.1016/j.coi.2009.03.009. Epub 2009 Apr 9.

Abstract

The four T cell receptor genes (Tcra, Tcrb, Tcrg, Tcrd) are assembled by V(D)J recombination according to distinct programs during intrathymic T cell development. These programs depend on genetic factors, including gene segment order and recombination signal sequences. They also depend on epigenetic factors. Regulated changes in chromatin structure, directed by enhancers and promoter, can modify the availability of recombination signal sequences to the RAG recombinase. Regulated changes in locus conformation may control the synapsis of distant recombination signal sequences, and regulated changes in subnuclear positioning may influence locus recombination events by unknown mechanisms. Together these influences may explain the ordered activation and inactivation of T cell receptor locus recombination events and the phenomenon of Tcrb allelic exclusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Gene Rearrangement, T-Lymphocyte*
  • Humans
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Recombination, Genetic
  • Signal Transduction
  • VDJ Exons / genetics
  • VDJ Recombinases / metabolism

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • VDJ Recombinases