title: Identification and physical mapping of a polymorphic human T cell receptor V beta gene with a frequent null allele.
abstract: 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.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena 91125.
authors.forename: P
authors.initials: P
authors.lastname: Charmley
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Hood
authors.forename: D A
authors.initials: DA
authors.lastname: Nickerson
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003062:Codon; D008040:Genetic Linkage; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012313:RNA / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
chemical_list: D003062:Codon; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA