Transient rearrangements of the T cell antigen receptor alpha locus in early thymocytes.

Abstract

The dull Ly-1 double-negative (Ly-1dull, Lyt-2-, L3T4-) subpopulation appears to be the major precursor group to T lymphocytes in the thymus. In exxamining 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., .fwdarw. J.gamma.C.gamma. gene rearrangements; with the .beta. chain genes, both D.beta. .fwdarw. J.beta.C.beta. rearrangement and V.beta. .fwdarw. 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 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. .fwdarw. J.alpha. joining. These distinctions between the character of the TCR gene rearrangements in these cells represent useful marders in further distinguishing different stages of T cell differentiation within this compartment of early T cells. In addition, the unexpected discovery of clonal rearragements 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.