Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1985 Mar 11;13(5):1607–1621. doi: 10.1093/nar/13.5.1607

Complete nucleotide sequence of a functional HLA-DP beta gene and the region between the DP beta 1 and DP alpha 1 genes: comparison of the 5' ends of HLA class II genes.

A Kelly, J Trowsdale
PMCID: PMC341099  PMID: 2987832

Abstract

The complete nucleotide sequence of an HLA-DP beta 1 gene and part of the adjacent DP alpha 1 gene, up to and including the signal sequence exon, were determined. The sequence of the DP beta 1 gene identified it as the DPw4 allele. The six exons of the DP beta 1 gene spanned over 11,000 bp of sequence. The arrangement of the gene was broadly analogous to genes of other class II beta chains. The beta 1 exon was flanked by introns of over 4 kb. Comparisons with published sequences of cDNA clones indicated that an alternative splice junction, at the 3' end of the gene, is used in at least one allele. Variation in choice of splice junction indicates an additional mechanism for allelic variation in class II genes. The sequence also indicated that the DP beta 1 and DP alpha 1 genes are separated by only 2 kb at their 5' ends. Comparison of the 5' ends of the DP alpha 1 and beta 1 genes with other class II sequences, including the DZ alpha gene, showed conservation of several blocks of sequences thought to be involved in control of expression. Some areas of the introns were partially conserved in the DQ beta gene, and several other intron sequences were homologous to sequences found in other unrelated genes.

Full text

PDF
1607

Selected References

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

  1. Auffray C., Ben-Nun A., Roux-Dosseto M., Germain R. N., Seidman J. G., Strominger J. L. Polymorphism and complexity of the human DC and murine I-A alpha chain genes. EMBO J. 1983;2(1):121–124. doi: 10.1002/j.1460-2075.1983.tb01392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boss J. M., Strominger J. L. Cloning and sequence analysis of the human major histocompatibility complex gene DC-3 beta. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5199–5203. doi: 10.1073/pnas.81.16.5199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Böhme J., Owerbach D., Denaro M., Lernmark A., Peterson P. A., Rask L. Human class II major histocompatibility antigen beta-chains are derived from at least three loci. Nature. 1983 Jan 6;301(5895):82–84. doi: 10.1038/301082a0. [DOI] [PubMed] [Google Scholar]
  4. Chang H. C., Moriuchi T., Silver J. The heavy chain of human B-cell alloantigen HLA-DS has a variable N-terminal region and a constant immunoglobulin-like region. 1983 Oct 27-Nov 2Nature. 305(5937):813–815. doi: 10.1038/305813a0. [DOI] [PubMed] [Google Scholar]
  5. Das H. K., Lawrance S. K., Weissman S. M. Structure and nucleotide sequence of the heavy chain gene of HLA-DR. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3543–3547. doi: 10.1073/pnas.80.12.3543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DeMars R., Chang C. C., Shaw S., Reitnauer P. J., Sondel P. M. Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens. Hum Immunol. 1984 Oct;11(2):77–97. doi: 10.1016/0198-8859(84)90047-8. [DOI] [PubMed] [Google Scholar]
  7. Falkner F. G., Zachau H. G. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. doi: 10.1038/310071a0. [DOI] [PubMed] [Google Scholar]
  8. Frayne E. G., Leys E. J., Crouse G. F., Hook A. G., Kellems R. E. Transcription of the mouse dihydrofolate reductase gene proceeds unabated through seven polyadenylation sites and terminates near a region of repeated DNA. Mol Cell Biol. 1984 Dec;4(12):2921–2924. doi: 10.1128/mcb.4.12.2921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gillies S. D., Folsom V., Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. doi: 10.1038/310594a0. [DOI] [PubMed] [Google Scholar]
  10. Grosschedl R., Birnstiel M. L. Spacer DNA sequences upstream of the T-A-T-A-A-A-T-A sequence are essential for promotion of H2A histone gene transcription in vivo. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7102–7106. doi: 10.1073/pnas.77.12.7102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gushima H., Yasuda S., Soeda E., Yokota M., Kondo M., Kimura A. Complete nucleotide sequence of the E. coli glutathione synthetase gsh-II. Nucleic Acids Res. 1984 Dec 21;12(24):9299–9307. doi: 10.1093/nar/12.24.9299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gustafsson K., Emmoth E., Widmark E., Böhme J., Peterson P. A., Rask L. Isolation of a cDNA clone coding for an SB beta-chain. Nature. 1984 May 3;309(5963):76–78. doi: 10.1038/309076a0. [DOI] [PubMed] [Google Scholar]
  13. Harvey R. P., Robins A. J., Wells J. R. Independently evolving chicken histone H2B genes: identification of a ubiquitous H2B-specific 5' element. Nucleic Acids Res. 1982 Dec 11;10(23):7851–7863. doi: 10.1093/nar/10.23.7851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hurley C. K., Shaw S., Nadler L., Schlossman S., Capra J. D. Alpha and beta chains of SB and DR antigens are structurally distinct. J Exp Med. 1982 Nov 1;156(5):1557–1562. doi: 10.1084/jem.156.5.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hyldig-Nielsen J. J., Schenning L., Hammerling U., Widmark E., Heldin E., Lind P., Servenius B., Lund T., Flavell R., Lee J. S. The complete nucleotide sequence of the I-E alpha d immune response gene. Nucleic Acids Res. 1983 Aug 11;11(15):5055–5071. doi: 10.1093/nar/11.15.5055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kappes D. J., Arnot D., Okada K., Strominger J. L. Structure and polymorphism of the HLA class II SB light chain genes. EMBO J. 1984 Dec 1;3(12):2985–2993. doi: 10.1002/j.1460-2075.1984.tb02245.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaufman J. F., Strominger J. L. HLA-DR light chain has a polymorphic N-terminal region and a conserved immunoglobulin-like C-terminal region. Nature. 1982 Jun 24;297(5868):694–697. doi: 10.1038/297694a0. [DOI] [PubMed] [Google Scholar]
  18. Kratzin H., Yang C. Y., Götz H., Pauly E., Kölbel S., Egert G., Thinnes F. P., Wernet P., Altevogt P., Hilschmann N. Primärstruktur menschlicher Histokompatibilitätsantigene der Klasse II. 1. Mitteilung: Aminosäuresequenz der N-terminalen 198 Reste der beta-Kette des HLA-Dw2,2;DR2,2-Alloantigens. Hoppe Seylers Z Physiol Chem. 1981 Dec;362(12):1665–1669. [PubMed] [Google Scholar]
  19. Kress M., Barra Y., Seidman J. G., Khoury G., Jay G. Functional insertion of an Alu type 2 (B2 SINE) repetitive sequence in murine class I genes. Science. 1984 Nov 23;226(4677):974–977. doi: 10.1126/science.6095445. [DOI] [PubMed] [Google Scholar]
  20. Larhammar D., Andersson G., Andersson M., Bill P., Böhme J., Claesson L., Denaro M., Emmoth E., Gustafsson K., Hammarling U. Molecular analysis of human class II transplantation antigens and their genes. Hum Immunol. 1983 Sep;8(1):95–103. doi: 10.1016/0198-8859(83)90087-3. [DOI] [PubMed] [Google Scholar]
  21. Lee J. S., Trowsdale J., Bodmer W. F. cDNA clones coding for the heavy chain of human HLA-DR antigen. Proc Natl Acad Sci U S A. 1982 Jan;79(2):545–549. doi: 10.1073/pnas.79.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Malissen M., Hunkapiller T., Hood L. Nucleotide sequence of a light chain gene of the mouse I-A subregion: A beta d. Science. 1983 Aug 19;221(4612):750–754. doi: 10.1126/science.6410508. [DOI] [PubMed] [Google Scholar]
  23. Mathis D. J., Benoist C. O., Williams V. E., 2nd, Kanter M. R., McDevitt H. O. The murine E alpha immune response gene. Cell. 1983 Mar;32(3):745–754. doi: 10.1016/0092-8674(83)90060-0. [DOI] [PubMed] [Google Scholar]
  24. Parslow T. G., Blair D. L., Murphy W. J., Granner D. K. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci U S A. 1984 May;81(9):2650–2654. doi: 10.1073/pnas.81.9.2650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pawelec G., Shaw S., Wernet P. Analysis of the HLA-linked SB gene system with cloned and uncloned alloreactive T-cell lines. Immunogenetics. 1982;15(2):187–198. [PubMed] [Google Scholar]
  26. Roux-Dosseto M., Auffray C., Lillie J. W., Boss J. M., Cohen D., DeMars R., Mawas C., Seidman J. G., Strominger J. L. Genetic mapping of a human class II antigen beta-chain cDNA clone to the SB region of the HLA complex. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6036–6040. doi: 10.1073/pnas.80.19.6036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Saito H., Maki R. A., Clayton L. K., Tonegawa S. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520–5524. doi: 10.1073/pnas.80.18.5520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  29. Sawada I., Beal M. P., Shen C. K., Chapman B., Wilson A. C., Schmid C. Intergenic DNA sequences flanking the pseudo alpha globin genes of human and chimpanzee. Nucleic Acids Res. 1983 Nov 25;11(22):8087–8101. doi: 10.1093/nar/11.22.8087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schenning L., Larhammar D., Bill P., Wiman K., Jonsson A. K., Rask L., Peterson P. A. Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains. EMBO J. 1984 Feb;3(2):447–452. doi: 10.1002/j.1460-2075.1984.tb01826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shackelford D. A., Kaufman J. F., Korman A. J., Strominger J. L. HLA-DR antigens: structure, separation of subpopulations, gene cloning and function. Immunol Rev. 1982;66:133–187. doi: 10.1111/j.1600-065x.1982.tb00437.x. [DOI] [PubMed] [Google Scholar]
  32. Shaw S., Kavathas P., Pollack M. S., Charmot D., Mawas C. Family studies define a new histocompatibility locus, SB, between HLA-DR and GLO. Nature. 1981 Oct 29;293(5835):745–747. doi: 10.1038/293745a0. [DOI] [PubMed] [Google Scholar]
  33. Singer D. S., Lifshitz R., Abelson L., Nyirjesy P., Rudikoff S. Specific association of repetitive DNA sequences with major histocompatibility genes. Mol Cell Biol. 1983 May;3(5):903–913. doi: 10.1128/mcb.3.5.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Spielman R. S., Lee J., Bodmer W. F., Bodmer J. G., Trowsdale J. Six HLA-D region alpha-chain genes on human chromosome 6: polymorphisms and associations of DC alpha-related sequences with DR types. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3461–3465. doi: 10.1073/pnas.81.11.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Springer T. A., Kaufman J. F., Terhorst C., Strominger J. L. Purification and structural characterisation of human HLA-linked B-cell antigens. Nature. 1977 Jul 21;268(5617):213–218. doi: 10.1038/268213a0. [DOI] [PubMed] [Google Scholar]
  36. Staden R. Automation of the computer handling of gel reading data produced by the shotgun method of DNA sequencing. Nucleic Acids Res. 1982 Aug 11;10(15):4731–4751. doi: 10.1093/nar/10.15.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trowsdale J., Kelly A., Lee J., Carson S., Austin P., Travers P. Linkage map of two HLA-SB beta and two HLA-SB alpha-related genes: an intron in one of the SB beta genes contains a processed pseudogene. Cell. 1984 Aug;38(1):241–249. doi: 10.1016/0092-8674(84)90546-4. [DOI] [PubMed] [Google Scholar]
  38. Trowsdale J., Lee J., Carey J., Grosveld F., Bodmer J., Bodmer W. Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1972–1976. doi: 10.1073/pnas.80.7.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ullrich A., Gray A., Goeddel D. V., Dull T. J. Nucleotide sequence of a portion of human chromosome 9 containing a leukocyte interferon gene cluster. J Mol Biol. 1982 Apr 15;156(3):467–486. doi: 10.1016/0022-2836(82)90261-3. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Wake C. T., Long E. O., Mach B. Allelic polymorphism and complexity of the genes for HLA-DR beta-chains--direct analysis by DNA-DNA hybridization. Nature. 1982 Nov 25;300(5890):372–374. doi: 10.1038/300372a0. [DOI] [PubMed] [Google Scholar]
  42. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wilson R., Storb U. Association of two different repetitive DNA elements near immunoglobulin light chain genes. Nucleic Acids Res. 1983 Mar 25;11(6):1803–1817. doi: 10.1093/nar/11.6.1803. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES