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Published January 1993 | Published
Journal Article Open

Identification and physical mapping of a polymorphic human T cell receptor V beta gene with a frequent null allele


Germline variation in genes that encode the human T cell receptors (TCRs) may have an important influence in shaping the immune T cell repertoire. In this report we describe a frequent null allele of the human V beta 18 gene, resulting from a nucleotide substitution that creates a stop codon (CGA<-->TGA). Approximately 11% of the population tested was homozygous for this null allele, indicating that this is a frequent "hole in the repertoire." We confirmed that there is a greatly reduced (undetectable) level of V beta 18 mRNA in peripheral blood lymphocytes from an individual homozygous for this null allele. In addition, all heterozygous individuals expressed detectable levels of only the functional V beta 18 allele in their peripheral blood lymphocytes. Two other DNA polymorphisms were identified in V beta 18, one of which would result in an amino acid substitution in an expressed V beta 18 gene. Genotypes for all three of these V beta 18 DNA polymorphisms were determined in a group of unrelated individuals. Statistical analyses of the associations between alleles of the V beta 18 polymorphisms and those of other DNA polymorphisms in the TCR beta locus suggested a close physical proximity between the V beta 18 gene and the 3' end of the C beta 2 region. This localization of human V beta 18 had been previously predicted by the sequence homology between human V beta 18 and mouse V beta 14, a V gene segment previously mapped to 3' of the mouse C beta genes. We confirmed this localization of the human V beta 18 gene by isolating a cosmid clone that contains both the V beta 18 and C beta 2 segments. Mapping by restriction enzyme digestion and by the polymerase chain reaction indicated that the V beta 18 gene segment is approximately 9 kb 3' of the C beta 2 gene, making this the only known human V beta gene 3' of the C beta region.

Additional Information

© 1993 by Rockefeller University Press. Received for publication 23 June 1992 and in revised form 2 October 1992. We thank Ms. Wendy Ankener and Ms. Patsy Byers for technical assistance and oligonucleotide syntheses, Drs. Jim Brawley, Patrick Concannon, Bill Funkhouser, Andy Herman, Ben Koop, Eric Milner, Jerry Nepom, and Dave Ostrov for helpful discussions and manuscript review. This work was supported by National Institutes of Health grants HG-00084 and DK-41347, the Whittier Foundation, and National Science Foundation grant DIR 8809710.

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