Polymorphism in human T cell receptor alpha chain variable region genes

Polymorphism of human T cell antigen receptor (TCR)alpha genes was detected by restriction fragment length polymorphism (RFLP). Individual TCR alpha gene segments showed limited polymorphism in that few restriction enzymes revealed polymorphism in genomic DNA samples and when RFLP were detected only two or three allelic forms were observed. A rabbit TCR alpha cDNA clone (VJR5) detected polymorphism in human DNA samples digested with PvuII or MspI. In order to characterize the human V alpha genes detected by the rabbit probe, genomic clones hybridizing with the VJR5 probe were isolated and characterized. A probe derived from a human genomic clone (HUTAVR5) hybridized with some but not all fragments detected by the rabbit VJR5 probe. The data suggest that the rabbit probe hybridized with two distinct human TCR alpha V genes and that polymorphism of each gene was detectable by only one restriction enzyme. In contrast to the limited polymorphism of TCR alpha genes detected by individual markers, extensive heterogeneity of TCR alpha genes was observed in the combination of markers present in haplotypes. Six RFLP were used as TCR alpha markers to define haplotypes in 20 parents and 53 offspring from 10 families and 17 different combinations of markers were observed. The observation that TCR alpha haplotypes include numerous combinations of markers that individually show limited polymorphism suggests that recombination may occur frequently within the TCR alpha gene complex.