title: Enforcing order within a complex locus: current perspectives on the control of V(D)J recombination at the murine T-cell receptor alpha/delta locus.
abstract: V(D)J recombination proceeds according to defined developmental programs at T-cell receptor (TCR) and immunoglobulin loci as a function of cell lineage and stage of differentiation. Although the molecular details are still lacking, such regulation is thought to occur at the level of accessibility of chromosomal recombination signal sequences to the recombinase. The unique and complex organization of the TCRalpha/delta locus poses intriguing regulatory challenges in this regard: embedded TCRalpha and TCRdelta gene segments rearrange at distinct stages of thymocyte development, there is a highly regulated progression of primary followed by secondary rearrangements involving Jalpha segments, and there are important developmental constraints on V gene segment usage. The locus therefore provides a fascinating laboratory in which to explore the basic mechanisms underlying developmental control. We provide here a current view of cis-acting mechanisms that enforce the TCRalpha/delta locus developmental program, and we emphasize the unresolved issues that command the attention of our and other laboratories.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. krang001@mc.duke.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Krangel
authors.forename: Juan
authors.initials: J
authors.lastname: Carabana
authors.forename: Iratxe
authors.initials: I
authors.lastname: Abbarategui
authors.forename: Ryan
authors.initials: R
authors.lastname: Schlimgen
authors.forename: Abbas
authors.initials: A
authors.lastname: Hawwari
mesh_terms: D000818:Animals; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D011995:Recombination, Genetic; D045567:VDJ Recombinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D045567:VDJ Recombinases