Skip to main content
Log in

A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR ser 57- asp 57 β )

  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The single DR beta chain gene of the DRw8 haplotype has been suggested to carry both the DRw8 and the DRw52 epitopes. Cellular typing has shown that the DRw8 haplotype can be split into three subtypes, Dw8.1. Dw8.2, and Dw8.3, presumably due to a polymorphism in the DRw8 β chain. Furthermore, Dw8.1 and Dw8.2 cells present influenza virus antigen to different T-cell clones. In the present study, DRw8/Dw8.2 β chain cDNA was cloned and characterized. A comparison of this sequence with a partial DRw8/Dw8.1 β chain gene suggested that the DRw8 split is due to a single amino acid replacement of ser 57 -asp 57 caused by three nucleotide substitutions in the same codon. In most DR haplotypes, two expressed DR beta chain genes exist. Comparing the nucleotide sequence of the single beta gene in the DRw8 haplotype to those of other DR beta genes revealed that the DRw8 beta gene sequence is most closely related to the DRBI genes of the DR3, 5, and w6 haplotypes. However, the comparisons also showed that it was not possible from sequence similarities to divide the DR beta genes into two or more distinct allelic series.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Albert, E. D., Baur, M. P., and Mayr, W. R. (eds.): Histocompatibility Testing 1984, Springer-Verlag, Berlin, Heidelberg, 1984

    Google Scholar 

  • Andersson, G., Larhammar, D., Widmark, E., Servenius, B., Peterson, P. A., and Rask, L..: Class II genes of the human major histocompatibility complex: organization and evolutionary relationship of the DRβ genes. J Biol Chem 262: 8748–8758, 1987

    Google Scholar 

  • Andersson, G., Lindblom, B., Andersson, L., Gorski, J., Mach, B., and Rask, L.: The single DR β gene of the DRw8 haplotype is closely related to the DR β3III gene encoding DRw52. Immunogenetics 28: 1–5, 1988

    Google Scholar 

  • Auffray, C. and Rougeon, F.: Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem 107: 303–314, 1980

    Google Scholar 

  • Baldwin, G. C., Mickelson, E. M., Hansen, J. A., Nisperos, B., Antonelli, P., Nepom, B. S., and Nepom, G. T.: Electrophoretic variation between class Il molecules expressed on HLA-DRw8 homozygous typing cells reveals multiple distinct haplotypes. Immunogenetics 21: 49–60, 1985

    Google Scholar 

  • Bell, J. I., Denney, D., Foster, L., Belt, T., Todd, J. A., and McDevitt, H. O.: Allelic variation in the DR subregion of the human major histocompatibility complex. Proc Natl Acad Sci USA 84: 6234–6238, 1987

    Google Scholar 

  • Benton, W. D. and Davis, R. W.: Screening λgt recombinant clones by hybridization to single plaques in situ. Science 196: 180–182, 1977

    Google Scholar 

  • Berdoz, J., Gorski, J., Termijtelen, A.-M., Dayer, J.-M., Irlé, C., Schendel, D., and Mach, B.: Constitutive and induced expression of the individual HLA-DRβ and α chain loci in different cell types. J Immunol 139: 1336–1341, 1987

    Google Scholar 

  • Bétuel, H., Gebuhrer, L., Schreuder, G. M. T., Layrisse, Z., ArnaizVillena, A., and Goldman, S. F.: HLA-DRw8 antigen report. In E. D. Albert, M. P. Baur, and W. R. Mayr (eds.): Histocompatibili ty Testing 1984, pp. 198–200, Springer Verlag, Berlin, Heidelberg, 1984

    Google Scholar 

  • Blobel, G. and Dobberstein, B.: Transfer of proteins across membranes. J Cell Biol 67: 835–851, 1975

    Google Scholar 

  • Böhme, J., Andersson, M., Andersson, G., Möller, E., Peterson, P. A., and Rask, L.: HLA DRβ genes vary in number between different DR specificities, whereas the number of DQβ genes is constant. J Immunol 135: 2149–2155, 1985

    Google Scholar 

  • Bouillot, M., Choppin, J., Sterkers, G., Freidel, C., Gebuhrer, L., Bétuel, H., and Levy, J. P.: The two-dimensional migration pattern of the single HLA-DR beta chain expressed in DRw8 haplotypes is not fully predictive of its activity in antigen presentation. Immunogenetics 28: 46–49, 1988

    Google Scholar 

  • Brégégère, F.: A directional process of gene conversion is expected to yield dynamic polymorphism associated with stability of alternative alleles in class I histocompatibility antigens gene family. Biochimie 65: 229–237, 1983

    Google Scholar 

  • Brown, J. H., Jardetzky, T., Saper, M. A., Samraoui, B., Björkman, P. J., and Wiley, D. C.: A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature 332: 845–850, 1988

    Google Scholar 

  • Bushell, A., Wood, K. J., and Morris, P. J.: DQ Wa gives rise to a DQβ restriction fragment pattern indistinguishable from that of the DQw3.2 subtype of DQw3. Tissue Antigens 32: 41–45, 1988

    Google Scholar 

  • Cairns, J. S., Curtsinger, J. M., Dahl, C. A., Freeman, S., Alter, B. J., and Bach, F. H.: Sequence polymorphism of HLA DRβ1 alleles relating to T-cell-recognized determinants. Nature 317: 166–168, 1985

    Google Scholar 

  • Claesson-Welsh, L. and Peterson, P. A.: Implications of the invariant γ-chain on the intracellular transport of class II histocompatibility antigens. J Immunol 135: 3551–3557, 1985

    Google Scholar 

  • Cullen, S. E. and Schwartz, B. D.: An improved method for isolation of H-2 and la alloantigens with immunoprecipitation induced by protein A-bearing staphylococci. J Immunol 117: 136–142, 1976

    Google Scholar 

  • Denaro, M., Hammerling, U., Rask, L., and Peterson, P. A.: The Eb β gene may have acted as the donor gene in a gene conversion-like event generating the Abm12 β mutant. EMBO J 3: 2029–2032, 1984

    Google Scholar 

  • Didier, D. K., Schiffenbauer, J., Shuman, S., Abruzzini, L. F., Gorski, J., Watling, D. L., Tieber, V. L., and Schwartz, B. D.: Characterization of two distinct DRβ chain alleles at the β III locus of the DR5 haplotype: βIII alleles are highly conserved. J Immunol 137: 2627–2631, 1986

    Google Scholar 

  • Feinberg, A. P. and Vogelstein, B.: A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137: 266–267, 1984

    Google Scholar 

  • Gorski, J. and Mach, B.: Polymorphism of human Ia antigens: gene conversion between two DR β loci results in a new HLA-D/DR specificity. Nature 322: 67–70, 1986

    Google Scholar 

  • Gorski, J., Rollini, P., and Mach, B.: Structural comparison of the genes of two HLA-DR supertypic groups: the loci encoding DRw52 and DRw53 are not truly allelic. Immunogenetics 25: 397–402, 1987a

    Google Scholar 

  • Gorski, J., Tilanus, M., Giphart, M., and Mach, B.: Oligonucleotide genotyping shows that alleles at the HLA-DRa βIII locus of the DRw52 supertypic group segregate independently of known DR or Dw specificities. Immunogenetics 25: 79–83, 1987b

    Google Scholar 

  • Gregersen, P. K., Shen, M., Song, Q.-L., Merryman, P., Degar, S., Seki, T., Maccari, J., Goldberg, D., Murphy, H., Schwenzer, J., Wang, C. Y., Winchester, R. J., Nepom, G. T., and Silver, J.: Molecular diversity of HLA-DR4 haplotypes. Proc Natl Acad Sci USA 83: 2642–2646, 1986

    Google Scholar 

  • Grosse-Wiley, H., Doxiadis, I., and Brandt, H.: Definition of HLA-D with HTC. In E. D. Albert, M. P. Baur, and W. R. Mayr (eds.): Histocompatibility Testing 1984, pp. 249–264, Springer-Verlag, Berlin, Heidelberg, 1984

    Google Scholar 

  • Gubler, U. and Hoffman, B. J.: A simple and very efficient method for generating cDNA libraries. Gene 25: 263–269, 1983

    Google Scholar 

  • Gustafsson, K., Wiman, K., Emmoth, E., Larhammar, D., Böhme, J., Hyldig-Nielsen, J.-J., Ronne, H., Peterson, P. A., and Rask, L.: Mutations and selection in the generation of class II histocompatibility antigen polymorphism. EMBO J. 3: 1655–1661, 1984

    Google Scholar 

  • Henin, Y., Sterkers, G., Gomard, E., Gebuhrer, L., Freidel, A. C., Lepage, V., Stern, M. H., Michon, J., Bétuel, H., and Levy, J. P.: Functional subdivision of HLA-DRw8 with influenza-specific cloned cell lines. Immunogenetics 22: 407–412, 1985

    Google Scholar 

  • Herrera, F., Layrisse, Z., Carreño, B., Quintero, M., Honeyman, M., Mickelson, E. M., and Tsuji, K.: Definition of Dw8.2 by primary and secondary mixed lymphocyte cultures. Hum Immunol 12: 9–21, 1985

    Google Scholar 

  • Irlé, C., Jaques, D., Tiercy, J.-M., Fuggle, S. V., Gorski, J., Termijtelen, A., Jeannet, M., and Mach, B.: Functional polymorphism of each of the two HLA-DR β chain loci demonstrated with antigen specific DR3 and DRw52 restricted T cell clones. J Exp Med 167: 853–872, 1988

    Google Scholar 

  • Jinks-Robertson, S. and Petes, T. D.: High-frequency meiotic gene conversion between repeated genes on nonhomologous chromosomes in yeast. Proc Natl Acad Sci USA 82: 3350–3354, 1985

    Google Scholar 

  • Jonsson, A.-K., Hyldig-Nielsen, J.-J., Servenius, B., Larhammar, D., Andersson, G., Jörgensen, F., Peterson, P. A., and Rask, L.: Class II genes of the human major histocompatibility complex: comparisons of the DQ and DX α and β genes. J Biol Chem 262: 8767–8777, 1987

    Google Scholar 

  • Klareskog, L., Trädgård, L., Lindblom, J. B., and Peterson, P. A.: Reactivity of a rabbit antiserum against highly purified HLA-DR antigens. Scand J Immunol 7: 199–208, 1978

    Google Scholar 

  • Korman, A. J., Ploegh, H. L., Kaufman, J. F., Owen, M. J., and Stromfinger, J. L.: Cell-free synthesis and processing of the heavy and light chains of HLA-DR antigens. J Exp Med 152: 65s-82s, 1980

    Google Scholar 

  • Kost, T. A., Theodorakis, N., and Hughes, S. H.: The nucleotide sequence of the chick cytoplasmic β-actin gene. Nucleic Acids Res 11: 8287–8301, 1983

    Google Scholar 

  • Kourilsky, P.: Molecular mechanisms for gene conversion in higher cells. Trends Genet 2: 60–63, 1985

    Google Scholar 

  • Kratzin, H., Götz, H., Thinnes, F. P., Kruse, T., Barnikol, H. U., Wernel, P., and Hilschmann, N.: Structure of human class II antigens expressed by a homozygous lymphoblastoid B cell line. In B. G. Solheim, E. Möller, and S. Ferrone (eds.): HLA Class II Antigens, pp. 49–70 Springer-Verlag, Berlin, Heidelberg, New York, Tokyo, 1986

    Google Scholar 

  • Kvist, S., Wiman, K., Claesson, L., Peterson, P. A., and Dobberstein, B.: Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens. Cell 29: 61–69, 1982

    Google Scholar 

  • Larhammar, D., Servenius, B., Rask, L., and Peterson, P. A.: Characterization of an HLA DRβ pseudogene. Proc Natl Acad Sci USA 82: 1475–1479, 1985

    Google Scholar 

  • Lechler, R. I., Ronchese, F., Braunstein, N. S., and Germain, R. N.: I-A restricted T cell antigen recognition. Analysis of the roles of A α and A β using DNA-mediated gene transfer. J Exp Med 163: 678–696, 1986

    Google Scholar 

  • Long, E. O., Wake, C. T., Gorski, J., and Mach, B.: Complete sequence of an HLA-DR β chain deduced from a cDNA clone and identification of multiple non-allelic DR β chain genes. EMBO J 2: 389–394, 1983

    Google Scholar 

  • Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning, Cold Spring Harbor, New York, 1982

    Google Scholar 

  • McIntyre, K. R. and Seidman, J. G.: Nucleotide sequence of mutant IAβ bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature 308: 551–553, 1984

    Google Scholar 

  • Mengle-Gaw, L. and McDevitt, H. O.: Genetics and expression of mouse Ia antigen. Anna Rev Immunol 3: 367–396, 1985

    Google Scholar 

  • Mickelson, E. M., Nisperos, B., Layrisse, Z., Kim, S. J., Thomas, E. D., and Hansen, J. A.: Analysis of the HLA-DRw8 haplotype: recognition by HTC typing of three distinct antigen complexes in Caucasians, Native Americans, and Orientals. Immunogenetics 17: 399–410, 1983

    Google Scholar 

  • Okayama, H. and Berg, P.: High-efficiency cloning of full-length cDNA. Mol Cell Biol 2: 161–170, 1982

    Google Scholar 

  • Rollini, P., Mach, B., and Gorski, J.: Linkage map of three HLA-DRβ chain genes: evidence for a recent duplication event. Proc Natl Acad Sci USA 82: 7197–7201, 1985

    Google Scholar 

  • Tabor, S. and Richardson, C. C.: DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Proc Natl Acad Sci USA 84: 4767–4771, 1987

    Google Scholar 

  • Todd, J. A., Acha-Orbea, H., Bell, J.I., Chao, N., Fronek, Z., Jacob, C. O., McDermott, M., Sinha, A. A., Timmerman, L., Steinman, L., and McDevitt, H. O.: A molecular basis for MHC class 11associated autoimmunity. Science 240: 1003–1009, 1988

    Google Scholar 

  • Vieira, J. and Messing, J.: The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene 19: 259–268, 1982

    Google Scholar 

  • Weiss, E. H., Mellor, A., Golden, L., Fahrner, K., Simpson, E., Hurst, J., and 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 events. Nature 301: 671–674, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jonsson, AK., Andersson, L. & Rask, L. A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR ser 57- asp 57 β ). Immunogenetics 29, 308–316 (1989). https://doi.org/10.1007/BF00352840

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00352840

Keywords

Navigation