Distinct contracted conformations of the Tcra/Tcrd locus during Tcra and Tcrd recombination.

Published

Journal Article

Studies have suggested that antigen receptor loci adopt contracted conformations to promote long-distance interactions between gene segments during V(D)J recombination. The Tcra/Tcrd locus is unique because it undergoes highly divergent Tcrd and Tcra recombination programs in CD4(-)CD8(-) double negative (DN) and CD4(+)CD8(+) double positive (DP) thymocytes, respectively. Using three-dimensional fluorescence in situ hybridization, we asked whether these divergent recombination programs are supported by distinct conformational states of the Tcra/Tcrd locus. We found that the 3' portion of the locus is contracted in DN and DP thymocytes but not in B cells. Remarkably, the 5' portion of the locus is contracted in DN thymocytes but is decontracted in DP thymocytes. We propose that the fully contracted conformation in DN thymocytes allows Tcrd rearrangements involving V(delta) gene segments distributed over 1 Mb, whereas the unique 3'-contracted, 5'-decontracted conformation in DP thymocytes biases initial Tcra rearrangements to the most 3' of the available V(alpha) gene segments. This would maintain a large pool of distal 5' V(alpha) gene segments for subsequent rounds of recombination. Thus, distinct contracted conformations of the Tcra/Tcrd locus may facilitate a transition from a Tcrd to a Tcra mode of recombination during thymocyte development.

Full Text

Duke Authors

Cited Authors

  • Shih, H-Y; Krangel, MS

Published Date

  • August 30, 2010

Published In

Volume / Issue

  • 207 / 9

Start / End Page

  • 1835 - 1841

PubMed ID

  • 20696701

Pubmed Central ID

  • 20696701

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20100772

Language

  • eng

Conference Location

  • United States