[Allelic polymorphism in the coding region of human T cell receptor V beta 12 gene]

Sequence substitutions in T cell antigen receptor (TCR) beta chains have been shown to have a profound impact upon the fine specificity of T lymphocytes. It is, therefore, of interest to characterize allelic variations in the TCR gene segments that assemble to encode TCR molecules. In the present report, the sensitive technique of single stranded conformational polymorphism (SSCP) was used to screen for allelic sequence variations in the coding region of TCR V beta 12 gene. TCR V beta 12 specific primers were used to PCR amplify and 32P label a 273bp segment of the variable (V) gene segment. Sequence differences between different allelic forms were detected by denaturation of the DNA and separation on a non-denaturing, high resolution acrylamide gel. Using this rapid approach, four alleles of the TCR V beta 12 gene were detected in a population of 90 ethnically diverse individuals. Correct Mendelian segregation of the four alleles was demonstrated in family studies (n = 23) and allele frequencies were 0.4722, 0.3166, 0.2056, and 0.0056 respectively. Sequence analysis revealed sequence differences of 1-3 nucleotides involving three separate codons. However, predicted amino acid sequences of all four alleles are identical. These data strongly suggest that the TCR V beta 12 protein sequence is highly conserved.