Detection and mapping of polymorphic KpnI alleles in the human T-cell receptor constant beta-2 locus

Southern blot analysis with human T-cell receptor (TcR) beta-chain specific cDNA probes revealed two novel allelic forms of the TcR beta-2 gene locus. Three different genotypes were noted based on the presence of polymorphic KpnI restriction fragments: I, 5.7 kb fragment only; II, 3.9 kb and 1.8 kb fragments only; III, all three polymorphic fragments. This hybridization pattern suggested that the presence or absence of a polymorphic KpnI site within the 5.7 kb fragment defines the two different allelic forms of the TcR beta chain locus. By Southern blot analysis of genomic DNA from T-cell lines with deleted C-beta-1 regions and computer-assisted restriction site mapping of germline and cDNA sequences of the C-beta-2 locus, the polymorphic KpnI site was localized at 24 bp 5' to the third exon of the C-beta-2 gene. It was determined that the polymorphic KpnI site and the earlier described polymorphic BglII site located 5' to the C-beta-2 gene are not co-inherited. No difference was noted in distribution of the KpnI genotypes and allelic frequencies between 26 normal individuals and 22 patients with systemic lupus erythematosus. However, this newly characterized polymorphism of the TcR locus should provide a useful tool to analyse the role of inherited genetic variations in the function of T lymphocytes under normal and pathological conditions.