Early in their development, most 7'cells become committed to the expression of one, and only one, TCR o~ f3 combination. How do T cells achieve this TCR allelic exclusion? This article discusses the configuration and expression of TCR e~ and f3 genes in mature T-cell lines and TCR elf3 transgenic mice, and proposes three nonexclusive models to account for the significant occurrence of T cells with two productive~ gene rearrangements.

T cells can be divided into two subsets on the basis of the structure of the T-cell antigen receptor (TCR). In the adult, most T cells express a TCR heterodimer consisting of an ix and a 13 chain, whereas a minor population express an alternative TCR made of one y and one 8 chain. Each of these four TCR chains includes a clonally variable (V) region. During intrathymic development, the genes encoding the TCR V regions are assembled via a series of ordered gene rearrangements 1. For instance, in T cells committed to the ix [3 lineage,[3 chain V genes are formed first through the assembly of single members from each of three discrete libraries of gene segments, denoted variable (V~), diversity (Dr3) and joining (/13)-Next, ix chain V genes are assembled from two separate libraries of gene segments called variable (V~) and joining (/,,). During V to J, V to D, or D to J recombination, the coding elements are imprecisely joined to each other; often, a few bases are removed from one or both extremities 2, 3. In some instances, variability at the junction is further amplified by the inclusion of extra bases that were not present in either of the precursor sequences. As a consequence, V (D) J joining events can result either in productive rearrangements that maintain an open reading frame throughout the gene, or in out-of-frame, nonproductive rearrangements.