We had previously demonstrated that several subclones derived from a CD3+, CD4-/CD8-, TCR-alpha beta+ murine T cell line have undergone secondary Valpha-Jalpha rearrangements at the TCR-alpha locus (1). In an effort to examine the molecular mechanism responsible for these Valpha-Jalpha replacements, the structures of TCR-alphacDNA prepared from both the parental and subcloned T cell lines have been determined. Here we report that: 1) the mechanism whereby the secondary rearrangements occur is a precise deletion event that involves germ-line Valpha genes 5' to the preexisting Valpha-Jalpha complex joining to Jalpha segments 3' of the preexisting complex deleting the region in between, 2) preexisting productive Valpha-Jalpha rearrangements of the parental line do not allelically exclude productive and nonproductive secondary rearrangements, 3) both productively rearranged TCR-alpha alleles of the parental cell line can undergo secondary rearrangements, 4) the presence of unrearranged germline Valpha transcripts in the parental line support an "accessibility" model of regulated lymphocyte receptor gene rearrangement. In addition, we present data which suggests that one of the subcloned lines has undergone a third rearrangement of one of its TCR-alpha alleles. One interpretation of these results is that T cells may have the ability to circumvent allelic exclusion at the TCR-alpha locus early in their ontogeny. This could provide T cells with an additional mechanism for generating an Ag receptor repertoire which is not found in B cells.
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Fondell et al. (1990) studied this question.