THE GENOMIC STRUCTURE OF HUMAN-V-BETA-6 T-CELL ANTIGEN RECEPTOR GENES

Six genomic clones were characterized containing members of the human V-beta-6 subfamily of T cell antigen receptor genes. There were four major findings. (a) New V-beta genes were discovered, including V-beta-6.10, V-beta-13.4, V-beta-13.5, and V-beta-5.5. (b) Members of the V-beta-13, V-beta-6, and V-beta-5 subfamilies cluster together in the V-beta locus and may have evolved through multiple duplication events of an ancestral cassette containing V-beta-13-V-beta-6-V-beta-5 genes. These V-beta subfamilies are used by an estimated one-third of T cells in humans and probably represent a highly useful component of the V-beta repertoire. (c) The promoters of V-beta-13, V-beta-6, and V-beta-5 genes contain conserved decamer motifs, but discrete differences were observed between promoters of different V-beta subfamilies, raising the question of different transcriptional control depending on V-beta subfamily usage. (d) The new V-beta-6.10 gene is probably a pseudogene, which may have been inactivated due to retro-transposition of Alu elements into its promoter region, a mutation affecting a highly conserved cysteine residue or mutations of the 3' recombinase signal sequence.