Transient rearrangements of the T cell antigen receptor alpha locus in early thymocytes.
The dull Ly-1 double-negative (Ly-1dull, Lyt-2-, L3T4-) subpopulation appears to be the major precursor group of T lymphocytes in the thymus. In examining the status of the alpha, beta, and gamma chain genes for T cell receptors (TCR) in this population of cells and hybridomas made from them, we find that all of these loci appear to begin DNA rearrangements in a nearly simultaneous fashion. In the case of the gamma genes, these involve V gamma----J gamma C gamma gene rearrangements; with the beta chain genes, both D beta----J beta C beta rearrangement and V beta----D beta J beta C beta rearrangements are evident; and in the case of the alpha locus, assayed in part by pulsed-field gel electrophoresis, they take the form of a novel series of rearrangements occurring 80 kb or more 5' to the C alpha gene. These alpha locus rearrangements are well away from any of the J alpha gene segments found in cDNA clones to date and are deleted in most mature thymocytes and functional T cell lines. Therefore they appear to represent a distinct class of rearrangement that occurs before V alpha----J alpha joining. These distinctions between the character of the TCR gene rearrangements in these cells represent useful markers in further distinguishing different stages of T cell differentiation within this compartment of early T cells. In addition, the unexpected discovery of clonal rearrangements so far away from any of the expressed J alpha gene segments, and at a stage where there is little or no stable C alpha RNA present, has interesting implications for the hierarchy of TCR gene expression.
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D015252:Deoxyribonucleases, Type II Site-Specific; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009693:Nucleic Acid Hybridization; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D004247:DNA; D004262:DNA Restriction Enzymes; C034510:CTCGAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific