Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(23):9422–9426. doi: 10.1073/pnas.86.23.9422

Allelic sequence variations in the hypervariable region of a T-cell receptor beta chain: correlation with restriction fragment length polymorphism in human families and populations.

M A Robinson 1
PMCID: PMC298508  PMID: 2574461

Abstract

Direct sequence analysis of the human T-cell antigen receptor (TCR) V beta 1 variable gene identified a single base-pair allelic variation (C/G) located within the coding region. This change results in substitution of a histidine (CAC) for a glutamine (CAG) at position 48 of the TCR beta chain, a position predicted to be in the TCR antigen binding site. The V beta 1 polymorphism was found by DNA sequence analysis of V beta 1 genes from seven unrelated individuals; V beta 1 genes were amplified by the polymerase chain reaction, the amplified fragments were cloned into M13 phage vectors, and sequences were determined. To determine the inheritance patterns of the V beta 1 substitution and to test correlation with V beta 1 restriction fragment length polymorphism detected with Pvu II and Taq I, allele-specific oligonucleotides were constructed and used to characterize amplified DNA samples. Seventy unrelated individuals and six families were tested for both restriction fragment length polymorphism and for the V beta 1 substitution. The correlation was also tested using amplified, size-selected, Pvu II- and Taq I-digested DNA samples from heterozygotes. Pvu II allele 1 (61/70) and Taq I allele 1 (66/70) were found to be correlated with the substitution giving rise to a histidine at position 48. Because there are exceptions to the correlation, the use of specific probes to characterize allelic forms of TCR variable genes will provide important tools for studies of basic TCR genetics and disease associations.

Full text

PDF
9422

Images in this article

9423Image
on p.9423
9424Image
on p.9424
9425Image
on p.9425
9425Image
on p.9425

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beall S. S., Concannon P., Charmley P., McFarland H. F., Gatti R. A., Hood L. E., McFarlin D. E., Biddison W. E. The germline repertoire of T cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis. J Neuroimmunol. 1989 Jan;21(1):59–66. doi: 10.1016/0165-5728(89)90159-8. [DOI] [PubMed] [Google Scholar]
  2. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Concannon P., Gatti R. A., Hood L. E. Human T cell receptor V beta gene polymorphism. J Exp Med. 1987 Apr 1;165(4):1130–1140. doi: 10.1084/jem.165.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Concannon P., Pickering L. A., Kung P., Hood L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6598–6602. doi: 10.1073/pnas.83.17.6598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  6. Ikuta K., Ogura T., Shimizu A., Honjo T. Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7701–7705. doi: 10.1073/pnas.82.22.7701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
  8. Lai E., Concannon P., Hood L. Conserved organization of the human and murine T-cell receptor beta-gene families. Nature. 1988 Feb 11;331(6156):543–546. doi: 10.1038/331543a0. [DOI] [PubMed] [Google Scholar]
  9. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  10. Robinson M. A., Kindt T. J. Molecular genotyping of human T-cell antigen receptor variable gene segments. Immunogenetics. 1986;24(4):259–266. doi: 10.1007/BF00364530. [DOI] [PubMed] [Google Scholar]
  11. Robinson M. A., Kindt T. J. Segregation of polymorphic T-cell receptor genes in human families. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3804–3808. doi: 10.1073/pnas.82.11.3804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  13. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Scharf S. J., Horn G. T., Erlich H. A. Direct cloning and sequence analysis of enzymatically amplified genomic sequences. Science. 1986 Sep 5;233(4768):1076–1078. doi: 10.1126/science.3461561. [DOI] [PubMed] [Google Scholar]
  15. Schiffer M., Wu T. T., Kabat E. A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4461–4463. doi: 10.1073/pnas.83.12.4461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seboun E., Robinson M. A., Doolittle T. H., Ciulla T. A., Kindt T. J., Hauser S. L. A susceptibility locus for multiple sclerosis is linked to the T cell receptor beta chain complex. Cell. 1989 Jun 30;57(7):1095–1100. doi: 10.1016/0092-8674(89)90046-9. [DOI] [PubMed] [Google Scholar]
  17. Seboun E., Robinson M. A., Kindt T. J., Hauser S. L. Insertion/deletion-related polymorphisms in the human T cell receptor beta gene complex. J Exp Med. 1989 Oct 1;170(4):1263–1270. doi: 10.1084/jem.170.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tillinghast J. P., Behlke M. A., Loh D. Y. Structure and diversity of the human T-cell receptor beta-chain variable region genes. Science. 1986 Aug 22;233(4766):879–883. doi: 10.1126/science.3755549. [DOI] [PubMed] [Google Scholar]
  19. Toyonaga B., Mak T. W. Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol. 1987;5:585–620. doi: 10.1146/annurev.iy.05.040187.003101. [DOI] [PubMed] [Google Scholar]
  20. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  21. Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES