Tandem linkage and unusual RNA splicing of the T-cell receptor β-chain variable-region genes

The variable-region (V) genes of the murine T-cell receptor β chain exist largely as single-element subfamilies. The V(β)5 and V(β)8 genes belong to the only two known three-member V(β) subfamilies. We present studies on the linkage of these six genes and show that the genomic organization is that of alternating V(β)5 and V(β)8 genes. Our analysis suggests that these genes were tandemly duplicated, the unit of duplication being a pair of V(β)5 and V(β)8 genes. This tandem organization permits transcripts to initiate from the promoter of an unrearranged V(β) located upstream of the rearranged V(β) gene. These transcripts can generate functional β-chain gene messages by novel RNA splicing of the upstream leader exon to the V(β) coding exon of the downstream rearranged gene. We extend the analysis of the T-cell receptor genomic organization to include 12 V(β) genes and suggest that all V(β) genes are closely linked on chromosome 6. In addition, we discuss the possible implications of the close linkage of the V(β) genes on the development of the T-cell receptor β-chain gene repertoire.