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 retrotransposition of Alu elements into its promoter region, a mutation affecting a highly conserved cysteine residue or mutations of the 3' recombinase signal sequence.

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