Hedgehog Signaling Regulates Differentiation from Double-Negative to Double-Positive Thymocyte

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 Vδ 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 Vα gene segments. This would maintain a large pool of distal 5′ Vα 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.

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Lateral shift of acoustic wave at interface between double-positive and double-negative media

Physics Letters A ◽

10.1016/j.physleta.2006.05.065 ◽

2006 ◽

Vol 358 (5-6) ◽

pp. 484-486 ◽

Cited By ~ 6

Author(s):

Lunwu Zeng ◽

Runxia Song

Keyword(s):

Acoustic Wave ◽

Lateral Shift ◽

Double Negative ◽

Double Positive

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Defined αβ T Cell Receptors with Distinct Ligand Specificities Do Not Require Those Ligands to Signal Double Negative Thymocyte Differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20032204 ◽

2004 ◽

Vol 199 (12) ◽

pp. 1719-1724 ◽

Cited By ~ 8

Author(s):

Batu Erman ◽

Terry I. Guinter ◽

Alfred Singer

Keyword(s):

T Cell ◽

T Cell Development ◽

Cell Receptor ◽

Peptide Ligands ◽

Double Negative ◽

Antigen Receptors ◽

Double Positive ◽

Recombination Activating Gene ◽

Thymocyte Differentiation ◽

Deficient Mice

During T cell development in the thymus, pre–T cell receptor (TCR) complexes signal CD4− CD8− (double negative [DN]) thymocytes to differentiate into CD4+ CD8+ (double positive [DP]) thymocytes, and they generate such signals without apparent ligand engagements. Although ligand-independent signaling is unusual and might be unique to the pre-TCR, it is possible that other TCR complexes such as αβ TCR or αγ TCR might also be able to signal the DN to DP transition in the absence of ligand engagement if they were expressed on DN thymocytes. Although αγ TCR complexes efficiently signal DN thymocyte differentiation, it is not yet certain if αβ TCR complexes are also capable of signaling DN thymocyte differentiation, nor is it certain if such signaling is dependent upon ligand engagement. This study has addressed these questions by expressing defined αβ TCR transgenes in recombination activating gene 2−/− pre-Tα−/− double deficient mice. In such double deficient mice, the only antigen receptors that can be expressed are those encoded by the αβ TCR transgenes. In this way, this study definitively demonstrates that αβ TCR can in fact signal the DN to DP transition. In addition, this study demonstrates that transgenic αβ TCRs signal the DN to DP transition even in the absence of their specific MHC–peptide ligands.

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