Skip to main content
PMC 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
. 1986 Apr;83(8):2642–2646. doi: 10.1073/pnas.83.8.2642

Molecular diversity of HLA-DR4 haplotypes.

P K Gregersen, M Shen, Q L Song, P Merryman, S Degar, T Seki, J Maccari, D Goldberg, H Murphy, J Schwenzer, et al.
PMCID: PMC323355  PMID: 3458223

Abstract

Complementary DNA (cDNA) clones encoding beta chains of the DR and DQ regions and alpha chains of the DQ region were isolated and sequenced from four homozygous DR4 cell lines of different HLA-D types: GM3103(Dw4), FS(Dw10), BIN(Dw14), and KT3(Dw15). When compared with each other and with a previously published sequence from a DR4 (Dw13 cell line), the variability of DR beta 1 gene products is generally restricted to the region around amino acid position 70, with an additional polymorphism at position 86. Many of these differences, including an unusual amino acid substitution at position 57 in the Japanese cell line KT3(Dw15), may be due to gene conversion events from the DR beta 2 or DX beta genes. In contrast, DR beta 2 molecules are identical in Dw15, Dw10, and Dw4 cell lines. DQ beta chains isolated from GM3103(Dw4), FS(Dw10), and BIN40(Dw14) are also identical. However, the DQ beta sequence from cell line KT3(Dw15) differs substantially from all other previously reported DQ beta alleles, consistent with its serological designation, DQ "blank." The first domain sequences of DQ alpha chains were identical in all four cell lines. The data suggest that relatively circumscribed amino acid changes in the DR beta 1 molecule are responsible for the HLA-D typing differences between some haplotypes.

Full text

PDF
2642

Selected References

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

  1. Auffray C., Lillie J. W., Arnot D., Grossberger D., Kappes D., Strominger J. L. Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes. Nature. 1984 Mar 22;308(5957):327–333. doi: 10.1038/308327a0. [DOI] [PubMed] [Google Scholar]
  2. Bell J. I., Denny D. W., Jr, McDevitt H. O. Structure and polymorphism of murine and human class II major histocompatibility antigens. Immunol Rev. 1985 Jul;84:51–71. doi: 10.1111/j.1600-065x.1985.tb01125.x. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Cairns J. S., Curtsinger J. M., Dahl C. A., Freeman S., Alter B. J., Bach F. H. Sequence polymorphism of HLA DR beta 1 alleles relating to T-cell-recognized determinants. Nature. 1985 Sep 12;317(6033):166–168. doi: 10.1038/317166a0. [DOI] [PubMed] [Google Scholar]
  5. Glisin V., Crkvenjakov R., Byus C. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 1974 Jun 4;13(12):2633–2637. doi: 10.1021/bi00709a025. [DOI] [PubMed] [Google Scholar]
  6. Götz H., Kratzin H., Thinnes F. P., Yang C., Kruse T., Pauly E., Kölbel S., Egert G., Wernet P., Hilschmann N. Primary structure of human class II histocompatibility antigens 3rd communication. Amino acid sequence comparison between DR and DC subclass antigens derived from a lymphoblastoid B cell line homozygous at the HLA loci (HLA-A3,3; B7,7; Dw2,2; DR2,2: MT1,1; Dc1,1: MB1,1). Hoppe Seylers Z Physiol Chem. 1983 Jun;364(6):749–755. doi: 10.1515/bchm2.1983.364.1.749. [DOI] [PubMed] [Google Scholar]
  7. Hochman P. S., Huber B. T. A class II gene conversion event defines an antigen-specific Ir gene epitope. J Exp Med. 1984 Dec 1;160(6):1925–1930. doi: 10.1084/jem.160.6.1925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holbeck S. L., Kim S. J., Silver J., Hansen J. A., Nepom G. T. HLA-DR4-associated haplotypes are genotypically diverse within HLA. J Immunol. 1985 Jul;135(1):637–641. [PubMed] [Google Scholar]
  9. Korman A. J., Boss J. M., Spies T., Sorrentino R., Okada K., Strominger J. L. Genetic complexity and expression of human class II histocompatibility antigens. Immunol Rev. 1985 Jul;85:45–86. doi: 10.1111/j.1600-065x.1985.tb01130.x. [DOI] [PubMed] [Google Scholar]
  10. Larhammar D., Hyldig-Nielsen J. J., Servenius B., Andersson G., Rask L., Peterson P. A. Exon-intron organization and complete nucleotide sequence of a human major histocompatibility antigen DC beta gene. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7313–7317. doi: 10.1073/pnas.80.23.7313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Larhammar D., Schenning L., Gustafsson K., Wiman K., Claesson L., Rask L., Peterson P. A. Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3687–3691. doi: 10.1073/pnas.79.12.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Larhammar D., Servenius B., Rask L., Peterson P. A. Characterization of an HLA DR beta pseudogene. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1475–1479. doi: 10.1073/pnas.82.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McIntyre K. R., Seidman J. G. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature. 1984 Apr 5;308(5959):551–553. doi: 10.1038/308551a0. [DOI] [PubMed] [Google Scholar]
  14. Mengle-Gaw L., Conner S., McDevitt H. O., Fathman C. G. Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant. J Exp Med. 1984 Oct 1;160(4):1184–1194. doi: 10.1084/jem.160.4.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moriuchi J., Moriuchi T., Silver J. Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications. Proc Natl Acad Sci U S A. 1985 May;82(10):3420–3424. doi: 10.1073/pnas.82.10.3420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nepom G. T., Nepom B. S., Antonelli P., Mickelson E., Silver J., Goyert S. M., Hansen J. A. The HLA-DR4 family of haplotypes consists of series of distinct DR and DS molecules. J Exp Med. 1984 Feb 1;159(2):394–404. doi: 10.1084/jem.159.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Norcross M. A., Kanehisa M. The predicted structure of the Ia beta 1 domain. A hypothesis for the structural basis of major histocompatibility complex-restricted T-cell recognition of antigens. Scand J Immunol. 1985 Jun;21(6):511–523. [PubMed] [Google Scholar]
  18. Okada K., Boss J. M., Prentice H., Spies T., Mengler R., Auffray C., Lillie J., Grossberger D., Strominger J. L. Gene organization of DC and DX subregions of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1985 May;82(10):3410–3414. doi: 10.1073/pnas.82.10.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reinsmoen N. L., Bach F. H. Five HLA-D clusters associated with HLA-DR4. Hum Immunol. 1982 Jun;4(3):249–258. doi: 10.1016/0198-8859(82)90040-4. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Segall M., Cairns J. S., Dahl C. A., Curtsinger J. M., Freeman S., Nelson P. J., Cohen O., Wu S., Nicklas J. N., Noreen H. J. DNA and protein studies of HLA class II molecules: their relationship to T cell recognition. Immunol Rev. 1985 Jul;85:129–148. doi: 10.1111/j.1600-065x.1985.tb01133.x. [DOI] [PubMed] [Google Scholar]
  23. Sorrentino R., Lillie J., Strominger J. L. Molecular characterization of MT3 antigens by two-dimensional gel electrophoresis, NH2-terminal amino acid sequence analysis, and southern blot analysis. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3794–3798. doi: 10.1073/pnas.82.11.3794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Spies T., Sorrentino R., Boss J. M., Okada K., Strominger J. L. Structural organization of the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5165–5169. doi: 10.1073/pnas.82.15.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Trowsdale J., Young J. A., Kelly A. P., Austin P. J., Carson S., Meunier H., So A., Erlich H. A., Spielman R. S., Bodmer J. Structure, sequence and polymorphism in the HLA-D region. Immunol Rev. 1985 Jul;85:5–43. doi: 10.1111/j.1600-065x.1985.tb01129.x. [DOI] [PubMed] [Google Scholar]
  27. Wallace R. B., Johnson M. J., Suggs S. V., Miyoshi K., Bhatt R., Itakura K. A set of synthetic oligodeoxyribonucleotide primers for DNA sequencing in the plasmid vector pBR322. Gene. 1981 Dec;16(1-3):21–26. doi: 10.1016/0378-1119(81)90057-3. [DOI] [PubMed] [Google Scholar]
  28. Weiss E. H., Mellor A., Golden L., Fahrner K., Simpson E., Hurst J., Flavell R. A. The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events. Nature. 1983 Feb 24;301(5902):671–674. doi: 10.1038/301671a0. [DOI] [PubMed] [Google Scholar]
  29. van Schravendijk M. R., Biddison W. E., Berger A. E., Coligan J. E. Comparative structural analysis of HLA-A3 antigens distinguishable by cytotoxic T lymphocytes: variant E1. J Immunol. 1985 Jan;134(1):410–416. [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