Organization of Human T-Cell Receptor β-Chain Genes: Clusters of VβGenes are Present on Chromosomes 7 and 9

To ascertain the extent and organization of the germ-line human T-cell receptor (TCR) β-chain gene repertoire, β-chain variable region (Vβ) genes were mapped by pulsed-field gel electrophoresis, cosmid cloning, and in situ hybridization. Probes derived from the 24 known Vβfamilies were mapped to a total of six Sfi I fragments in DNA samples from multiple individuals representing all possible haplotypes of TCR V-and C (constant)-region insertion/deletion-related polymorphisms. Four of the Sfi I fragments were linked to one another to develop an extended map of the TCR β-chain gene complex previously localized to chromosome 7q35. The remaining two Sfi I fragments, containing 6 Vβgenes, could not be linked to the TCR β-chain gene complex. Using human-hamster somatic cell hybrids and in situ hybridization, these orphon genes were localized to chromosome 9p. Nucleotide sequences of the orphon Vβgenes, derived from cosmid clones, were 93-97% identical to Vβgenes in the TCR β-chain gene complex. Open reading frames in three of the orphon Vβgenes were intact as were the recombination signal sequences. As expected, based on their orphon status, none of the Vβgenes of chromosome 9 was detected in transcripts containing Cβ. These results indicate that the functional germ-line Vβrepertoire in humans is substantially (10%) smaller than previously estimated.