IDENTIFICATION OF A DNA SEGMENT EXHIBITING REARRANGEMENT MODIFYING EFFECTS UPON TRANSGENIC DELTA-DELETING ELEMENTS

Control of the rearrangement and expression of the T cell receptor alp ha and delta chains is critical for determining T cell type. The proce ss of delta deletion is a candidate mechanism for maintaining separati on of the alpha and delta loci. Mice harboring a transgenic reporter d elta deletion construct show alpha/beta 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-specifi c rearrangement control of transgenic elements, with abundant rearrang ements of transgenic delta-deleting elements now in gamma/delta T cell s. Furthermore, HPS1A augments recombination frequency of extrachromos omal substrates in an in vitro recombination assay. DNA binding protei ns recognizing HPS1A have been identified and are restricted to early B and T cells, during the time of active rearrangement of endogenous T CR and immunoglobulin loci. These data are consistent with delta delet ion playing an important role in maintaining separate TCR alpha and de lta loci.