Molecular determination of T-cell receptor alpha and beta chain genotypes in human families.

Polymorphism in genes encoding the alpha and beta chain of the human T cell receptor has been detected by Southern blot analysis. Genomic DNA samples were isolated from B lymphoblastoid cell lines derived from members of families, each family including at least one individual with a recombinant HLA haplotype. T cell receptor alpha and beta chain haplotypes could be assigned in the families on the basis of observed restriction fragment length polymorphism (RFLP). Polymorphism in the alpha chain gene was detected in BglII digests using an alpha chain probe that included the V, J, C, and 3' untranslated sequences. A probe consisting of only the constant region (C alpha) revealed no polymorphism indicating that the polymorphic fragment hybridized to V, J, or 3' untranslated sequences of the alpha chain. Polymorphism in beta chain genes was observed in BglII digested DNA samples using a probe that corresponds to the constant region (C beta). Polymorphic C beta restriction fragments of 10.0 and 9.2 kilobase segregated in six of the eight families studied. Recent structural data for the C beta region suggest that the polymorphic BglII site lies in the region 5' to the C beta 2 gene. These polymorphisms should serve as markers for alpha and beta chain complexes allowing genetic studies of these immunologically important gene families.