Identification of a DNA Segment Exhibiting Rearrangement Modifying Effects upon Transgenic d - deleting Elements

Control of the rearrangement and expression of the T cell receptor a and d chains is critical for determining T cell type. The process of d deletion is a candidate mechanism for maintaining separation of the a and d loci. Mice harboring a transgenic reporter d deletion construct show a / b T cell lineage–specific use of the transgenic elements. A 48-basepair segment of DNA, termed HPS1A, when deleted from this reporter construct, loses tight lineage-specific rearrangement control of transgenic elements, with abundant rearrangements of transgenic d -deleting elements now in g / d T cells. Furthermore, HPS1A augments recombination frequency of extrachromosomal substrates in an in vitro recombination assay. DNA binding proteins recognizing HPS1A have been identified and are restricted to early B and T cells, during the time of active rearrangement of endogenous TCR and immunoglobulin loci. These data are consistent with d deletion playing an important role in maintaining separate TCR a and d loci.