Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Sequence analysis of the DRB1 promoter reveals limited polymorphism with no influence on gene expression

Genes & Immunity volume 2, pages 211–215 (2001)Cite this article

Abstract

HLA-class II promoters contain a set of conserved regulatory regions necessary for constitutive and induced gene expression. For the HLA-DQB as well as for the DRB1 promoter sequence, polymorphisms with influence on gene expression have been reported. In contrast to these data we could show that there is very limited allele-specific polymorphism among the HLA-DRB1 promoter alleles. In a long range PCR we amplified a DNA sequence containing the promoter and the second exon of the DRB1 gene in one fragment. Nested PCR products of this PCR fragment for the promoter and for the second exon were analysed by DNA sequencing to allow the linkage of a promoter to its DR allele. Most investigated DRB1 alleles exhibited the same promoter consensus sequence except for two point mutations. An A to T transversion (position −70 bp) was closely associated with DRB1*08, whereas a C-deletion (position −30 bp) was most commonly observed together with DRB1*10. Both polymorphisms did not influence promoter activity in luciferase reporter gene assays.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Böhme J, Andersson M, Andersson G, Möller E, Peterson PA, Rask I HLA-DR beta genes vary in number between different DR specifities, whereas the number of DQ beta genes is constant J Immunol 1985 135 2149–2155

    PubMed  Google Scholar 

  2. Rask L, Andersson G, Andersson L et al Generation of class II antigen polymorphism Immunol Rev 1985 84 123–143

    Article  CAS  Google Scholar 

  3. Bontrop R, Ottenhoff T, van Miltenburg R, Elferink D, de Vries R, Giphart M Quantitative and qualitve differences in HLA-DR molecules correlated with antigen presentation capacity Eur J Immunol 1986 16 133–138

    Article  CAS  Google Scholar 

  4. Irle C, Jaques D, Tiercy JM et al Functional polymorphism of each of the two HLA-DRβ chain loci demonstrated with antigen-specific DR3- and DRw52-restricted T-cell clones J Exp Med 1988 167 853–872

    Article  CAS  Google Scholar 

  5. Janeway CA, Bottomly K, Babich J et al Quantitative variation in Ia antigen expression plays a central role in immune regulation Immunol Today 1984 5 99–105

    Article  CAS  Google Scholar 

  6. Murray SM How the MHC selects Th1/Th2 immunity Immunol Today 1998 19 157–163

    Article  CAS  Google Scholar 

  7. Perfetto C, Zacheis M, McDaid D, Meador III JW, Schwartz BD Polymorphism in the promoter region of HLA-DRB genes Hum Immunol 1993 36 27–33

    Article  CAS  Google Scholar 

  8. Emery P, Mach B, Reith W The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequence Hum Immunol 1993 38 137–147

    Article  CAS  Google Scholar 

  9. Louis P, Eliaou J-F, Kerlan-Candom S, Pinet V, Vincent R, Clot J Polymorphism in the regulatory region of HLA-DRB genes correlating with haplotype evolution Immunogenetics 1993 38 21–26

    Article  CAS  Google Scholar 

  10. Louis P, Vincent R, Cavadore P, Clot J, Eliaou J-F Differential transcriptional activities of HLA-DR genes in various haplotypes J Immunol 1994 153 5059–5067

    CAS  PubMed  Google Scholar 

  11. Singal DP, Qiu X, D’Souza M, Sood SK Polymorphism in the upstream regulatory regions of HLA-DRB genes Immunogenetics 1993a 37 143–147

    Article  CAS  Google Scholar 

  12. Singal DP and Qiu X Polymorphism in the upstream regulatory region and level of expression of HLA-DRB genes Molec Immunol 1994 31 1117–1120

    Article  CAS  Google Scholar 

  13. Singal DP, Qiu X Polymorphism in both X and Y box motifs controls level of expression of HLA-DRB1 genes Immunogenetics 1995 43 50–56

    Article  Google Scholar 

  14. Barnes WM PCR amplification of up to 35-kb DNA with high fidelity and high yield from λ-bacteriophage template Proc Natl Acad Sci USA 1994 91 2216

    Article  CAS  Google Scholar 

  15. Cheng S, Fockler C, Barnes WM, Higuchi R Effective amplification of long targets from cloned inserts and human genomic DNA Proc Natl Acad Sci USA 1994 91 5694–5699

    Google Scholar 

  16. Benoist C, Mathis D Regulation of major histocompatibility complex class II genes: X, Y and other letters of the alphabet Annu Rev Immunol 1990 8 681–715

    Article  CAS  Google Scholar 

  17. Glimcher LH, Kara CJ Sequences and factors. A guide to MHC class II transcription Ann Rev Immunol 1992 10 13–49

    Article  CAS  Google Scholar 

  18. Andersen LC, Beaty JS, Andersen LC, Nepom GT Allelic polymorphism in transcriptional regulatory regions of HLA-DQB genes J Exp Med 1991 173 181–192

    Article  CAS  Google Scholar 

  19. Don RH, Cox PT, Wainright BJ, Baker K, Mattick JS ‘Touchdown’ PCR to circumvent spurious priming during gene amplification Nucl Acids Res 1991 19 4008

    Article  CAS  Google Scholar 

  20. Mullis KB, Faloona F Specific synthesis of DNA in vitro via a polymerase-catalysed chain reaction Methods Enzymol 1987 155 335–350

    Article  CAS  Google Scholar 

  21. Sanger F, Nicklen S, Coulsen AR DNA sequencing with chain-terminating inhibitors Proc Natl Acad Sci USA 1977 74 5463–5467

    Article  CAS  Google Scholar 

  22. Schneider PM Molekulargenetische Untersuchungen zur Struktur der Gene der vierten Komponente des humanen Komplementsystems Thesis 1987 Johannes Gutenberg University, Mainz

    Google Scholar 

  23. Chu X, Braun-Heimer L, Rittner C, Schneider PM Identification of the recombination site within the steroid 21-hydroxylase gene (CYP21) of the HLA-B47,DR7 haplotype Exp Clin Immunogenet 1992 9 80–85

    CAS  PubMed  Google Scholar 

  24. Sambrook J, Fritsch EF, Maniatis T Molecular cloning: A laboratory manual Cold Spring Harbor Laboratory, Cold Spring Harbor 1989

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Legal Medicine, Johannes Gutenberg-University, Mainz, Germany

    A Kruger, PM Schneider & C Rittner

  2. 1st Medical Clinic, Johannes Gutenberg-University, Mainz, Germany

    P Quack & T Höhler

Authors
  1. A Kruger
    View author publications

    Search author on:PubMed Google Scholar

  2. P Quack
    View author publications

    Search author on:PubMed Google Scholar

  3. PM Schneider
    View author publications

    Search author on:PubMed Google Scholar

  4. C Rittner
    View author publications

    Search author on:PubMed Google Scholar

  5. T Höhler
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to T Höhler.

Additional information

This study was supported by a grant from the Deutsche Forschungsgemeinschaft (SFB490/A3).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kruger, A., Quack, P., Schneider, P. et al. Sequence analysis of the DRB1 promoter reveals limited polymorphism with no influence on gene expression . Genes Immun 2, 211–215 (2001). https://doi.org/10.1038/sj.gene.6363769

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.gene.6363769

Keywords

This article is cited by

Search

Advanced search

Quick links