Organization of human T-cell receptor beta-chain genes: clusters of V beta genes are present on chromosomes 7 and 9.
To ascertain the extent and organization of the germ-line human T-cell receptor (TCR) beta-chain gene repertoire, beta-chain variable region (V beta) genes were mapped by pulsed-field gel electrophoresis, cosmid cloning, and in situ hybridization. Probes derived from the 24 known V beta families 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 beta-chain gene complex previously localized to chromosome 7q35. The remaining two Sfi I fragments, containing 6 V beta genes, could not be linked to the TCR beta-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 V beta genes, derived from cosmid clones, were 93-97% identical to V beta genes in the TCR beta-chain gene complex. Open reading frames in three of the orphon V beta genes were intact as were the recombination signal sequences. As expected, based on their orphon status, none of the V beta genes of chromosome 9 was detected in transcripts containing C beta. These results indicate that the functional germ-line V beta repertoire in humans is substantially (10%) smaller than previously estimated.
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852.
M A
MA
Robinson
M P
MP
Mitchell
S
S
Wei
C E
CE
Day
T M
TM
Zhao
P
P
Concannon
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D003360:Cosmids; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017353:Gene Deletion; D015723:Gene Library; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D005838:Genotype; D006801:Humans; D006822:Hybrid Cells; D017403:In Situ Hybridization; D007621:Karyotyping; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015183:Restriction Mapping; D014158:Transcription, Genetic
D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA