Abstract
A cosmid clone containing the DRα gene and a β 1 exon of a DR β -related gene was isolated from a human cosmid clone bank made from the consanguineous DR7 cell line MANN. No other DRβ-related exons were found on this clone. The β 1 exon was located about 15 kb away from the DR α gene in a tail-to-tail (3′ to 3′) orientation. The exon contained several deleterious mutations: a defective splice site at the 5′ end, two translational frame shifts (a 1 by deletion and a 1 bp insertion), and three extra cysteine residues. Nucleotide and amino acid sequence comparisons of the β 1 exon indicated that although it is substantially different from other class II β-chain genes, it is slightly more related to DR than to any other class 11 gene. The DRβ-related sequence was on a DNA fragment which showed no polymorphism on a panel of cell lines with Eco RI or Pst 1. These Southern blots, however, revealed a related, polymorphic sequence in the human genome. Nucleotide sequences in the intron flanking the β 1 exon shared greater sequence homology than the β 1 exon itself when compared with the DR β genomic sequence. The exon may play a role in the generation of variation in expressed class II β-chain genes and it may be a relic of a different subset of class II products.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Auffray, C., Ben-Nun, A., Roux-Dossetto, M., Germain, R. N., Seidman, J. G., and Strominger, J. L.: Polymorphism and complexity of the human DC and murine I-A α chain genes. EMBO J. 2: 121–124, 1983
Bankier, A. T. and Barrell, B. G.: Shotgun DNA sequencing In H. L. Kornberg (ed.): Techniques in Life Sciences, Nucleic Acid Biochemistry, pp. 1–34, Elsevier Scientific Publishers, County Clare, Ireland, 1983
Bell, J. I., Estess, P., St.-John, T., Saiki, R., Watling, D. L., Erlich, A. A., and McDevitt, H. O.: DNA sequence and characterization of human class II major histocompatibility complex β chains from the DR1 haplotype. Proc. Natl. Acad. Sci. U.S.A. 82: 3405–3409, 1985
Bodmer, J. and Bodmer, W. F.: Histocompatibility 1984. Immunol. Today 5: 251–254, 1984
Bodmer, W. F., Bodmer, J., Lee, J., Spielman, R., Travers, P., and Trowsdale, J.: Structure, evolution and polymorphism of the HLA-D region. In T. Sasazuki and T. Tada (eds.): Immuno genetics — Its Applications to Clinical Medicine, pp. 263–281, Academic Press, Tokyo, 1984
Boss, J. M. and Strominger, J. L.: Cloning and sequence analysis of a DC-3β gene. Proc. Natl. Acad. Sci. U.S.A. 81: 5199–5203, 1984
Breathnach, R. and Chambon, P.: Organization and expression of eucaryotic split genes coding for proteins. Annu. Rev. Biochem. 50: 349–383, 1981
Chang, H. C., Moriuchi, T., and Silver, J.: The heavy chain of human β-cell alloantigen HLA-DS has a variable N-terminal region and a constant immunoglobulin-like region. Nature 301: 813–815, 1983
Das, H. K., Lawrance, S. K., and Weissman, S. M.: Structure and nucleotide sequence of the heavy chain gene of HLA-DR. Proc. Natl. Acad. Sci. U.S.A. 80: 3543–3547, 1983
Falkner, F. G. and Zachau, H. G.: Correct transcription of an immunoglobulin K gene required an upstream fragment containing conserved sequence elements. Nature 310: 71–74, 1984
Gillies, S. D., Folsom, V., and Tonegawa, S.: Cell specific enhancer element associated with a mouse MHC gene, Eβ. Nature 310: 594–597, 1984
Grosveld, F. G., Lund, T., Murray, E. J., Mellor, A. L., Dahl, H. H. M., and Flavell, R. A.: The construction of cosmid libraries which can be used to transform eukaryotic cells. Nucleic Acids Res. 10: 6715–6732, 1982
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
Hyldig-Nielsen, J.J., Schenning, L., Hammerling, U., Widmark, E., Heldin, E., Lind, P., Servinius, B., Lund, T., Flavell, R., Lee, J. S., Trowsdale, J., Schreier, P. H., Zablitzky, F., Larhammar, D., Peterson, P. A., and Rask, L.: The complete nucleotide sequence of the I-Eα d immune response gene. Nucleic Acids Res. 11: 5055–5071, 1983
Kappes, D. J., Arnot, D., Okada, K., and Strominger, J. L.: Structure and polymorphism of the HLA class II SB light chain genes. EMBO J. 3: 2985–2993, 1984
Kaufman, J. F. and Strominger, J. L.: HLA-DR light chain has a polymorphic N-terminal region and a conserved Ig-like C-terminal region. Nature 297: 694–697, 1982
Kelly, A. and Trowsdale, J.: Complete nucleotide sequence of a functional HLA-DPβ gene and the region between the DPβ1 and DPα1 genes: Comparison of the 5\ ends of HLA class II genes. Nucleic Acids Res. 13: 1607–1621, 1985
Klobeck, H. G., Combriato, G., and Zachau, H. G.: Immunoglobulin genes of the kappa light chain type from two human lymphoid cell lines are closely related. Nucleic Acids Res. 12: 6995–7006, 1984
Korman, A. J., Boss, J. M., Spies, T., Sorrentino, R., Okada, K., and Strominger, J. L.: Genetic complexity and expression of human class II histocompatibility antigens. Immunol. Rev. 85: 45–86, 1985
Kratzin, H., Yang, C., Götz, H., Pauly, E., Köbel, S., Egert, G., Thinnes, F., Wernet, P., Altevogt, P., and Hilschmann, N.: Primärstruktur menschlicher Histokompatibilitätsantigen der Klasse II. Hoppe-Seylers Z. Physiol. Chem. 362: 1665–1669, 1981
Larhammar, D., Hyldig-Nielsen, J. J., Servenius, B., Andersson, G., Rask, L., and Peterson, P. A.: Exon-intron organization and complete nucleotide sequence of a human major histocompatibility antigen DCβ gene. Proc. Nail. Acad. Sci. U.S.A. 80: 7313–7317, 1983a
Larhammar, D., Hammerling, U., Denaro, M., Lund, T., Flavell, R. A., Rask, L., and Peterson, P. A.: Structure of the murine immune response I-A β locus: Sequence of the I-A β gene and an adjacent β-chain second domain exon. Cell 34: 179–188, 1983b
Larhammar, D., Servenius, B., Rask, L., and Peterson, P. A.: Characterization of an HLA-DRβ pseudogene. Proc. Natl. Acad. Sci. U.S.A. 82: 1475–1479, 1985
Lee, J. S., Trowsdale, J., Travers, P., Carey, J., Grosveld, F., Jenkins, J., and Bodmer, W. F.: Sequence of an HLA-DR α-chain cDNA clone and intron-exon organization of the corresponding gene. Nature 299: 750–752, 1982
Long, E., Wake, C. T., Gorski, J., and Mach, B.: Complete sequence of an HLA-DRβ chain deduced from a cDNA clone and identification of multiple non allelic DRβ chain genes. EMBO J. 2: 389–394, 1983
Maeda, N., Yang, F., Barnett, D. R., Bowman, B. H., Smithies, O.: Duplication within the haptoglobin Hp 2 gene. Nature 309: 131–135, 1984
Malissen, M., Hunkapiller, T., and Hood, L.: Nucleotide sequence of a light chain gene of the mouse I-A subregion Aβ d. Science 221: 750–754, 1983
Mekalanos, J. J., Swartz, D. J., Pearson, G. D. N., Harford, N., Groyne, F., and de Wilde, M.: Cholera toxin genes: Nucleotide sequence deletion analysis and vaccine development. Nature 306: 551–557, 1983
Mengle-Gaw, L. and McDevitt, H. O.: Isolation and characterization of a cDNA clone for the murine I-Eβ polypeptide chain. Proc. Nod. Acad. Sci. U.S.A. 80: 7621–7625, 1983
Okada, K., Boss, J. M., Prentice, H., Spies, T., Mengler, R., Auffray, C., Lillie, J., Grossberger, D., and Strominger, J.: Gene organization of DC and DX subregions of the human major histocompatibility complex. Proc. Natl. Acad. Sci. U.S.A. 82: 3410–3414, 1985
Parslow, T. G., Blair, D. L., Murphy, W. J., and Granner, D. K.: Structure of the 5′ ends of immunoglobulin genes: A novel conserved sequence. Proc. Natl. Acad. Sci. U.S.A. 81: 2650–2654, 1984
Perler, F., Efstratiadis, A., Lomedico, P., Giblert, W., Kolodner, S., and Dodgson, J.: The evolution of genes: The chicken preproinsulin gene. Cell 20: 555–566, 1980
Rigby, P. W. J., Dieckmann, M., Rhodes, C., and Berg, P.: Labelling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymelase I. J. Mol. Biol. 113: 237–251, 1977
Saito, H., Maki, R. A., Clayton, L. K., and Tonegawa, S.: Complete primary structure of the Eβ chain and gene of the mouse major histocompatibility complex. Proc. Natl. Acad. Sci. U.S.A. 80: 5520–5524, 1983
Sanger, F., Coulson, A. R., Barrell, B. G., Smith, A. J. H., and Roe, B. A.: Cloning in single stranded bacteriophage as an aid to rapid DNA sequencing. J. Mol. Biol. 143: 161–178, 1980
Shackelford, D. A., Kaufman, J. F., Korman, A. J., and Strominger, J. L.: HLA-DR antigens: Structure, separation of subpopulations, gene cloning and function. Immunol. Rev. 66: 133–187, 1982
Snary, D., Barnstable, C., Bodmer, W. F., Goodfellow, P., and Crumpton, M. J.: Human Ia antigen purification and molecular structure. Cold Spring Harbor Symp. Quant. Biol. 41: 379–386, 1976
So, A. K. L., Trowsdale, J., Bodmer, J. G., and Bodmer, W. F.: DNA polymorphism of HLA-DRβ and HLA-DPβ genes. In E. D. Albert, M.P. Baur, and W.R. Mayr (eds.): Histocompatibility Testing 1984, pp. 565–568, Springer-Verlag, Berlin, 1984
Spielman, R. S., Lee, J. S., Bodmer, W. F., Bodmer, J. G., and Trowsdale, J.: Six HLA-Dα chain genes on human chromosome 6: Polymorphism and association of DCα-related sequence with DR types. Proc. Natl. Acad. Sci. U.S.A. 81: 3461–3465, 1984
Spies, T., Sorrentino, R., Boss, J. M., Okada, K., and Strominger, J. L.: Structural organization of the DR subregion of the human major histocompatibility complex. Proc. Natl. Acad. Sci. U.S.A. 82: 165–5169, 1985
Springer, T. A., Kaufman, J. F., Terhorst, C., and Strominger, J. L.: Purification and structural characterization of human HLA-linked B-cell antigens. Nature 268: 213–218, 1977
Stanway, G., Cann, A. J., Hauptmann, R., Hughes, P., Clarke, L. D., Mountfort, R. C., Minor, P. D., Schild, G. C., and Almond, J. W.: The nucleotide sequence of poliovirus type 3 loc 12 a1b: Comparison with polivirus type 1. Nucleic Acids Res. 11: 5629–5643, 1983
Thomas, P. S.: Hybridization of denatured RNA transferred or dotted to nitrocellulose paper. Methods Enzymol. 100: 255–265, 1983
Trowsdale, J., Lee, J., Carey, J., Grosveld, F., Bodmer, J., and Bodmer, W. F.: Sequences related to HLA-DRα chain on human chromosome 6: Restriction enzyme polymorphism detected with DCα chain probes. Proc. Natl. Acad. Sci. U.S.A. 80: 1972–1976, 1983a
Trowsdale, J., Lee, J., and Bodmer, W. F.: Genes in the HLA-D region of human chromosome 6. In J. W. Parker and R. L. O'Brien (eds.): Intercellular Communication in Leukocyte Function, pp. 367–372, John N. Wiley and Sons Ltd., New York, 1983b
Trowsdale, J., Kelly, A., Lee, J., Carson, S., Austin, P., and Travers, P.: Linkage map of two HLA-SB# and two HLA-SBα-related genes: An intron in one of the SBβ genes contains a processed pseudogene. Cell 38: 241–249, 1984
Trowsdale, J., Young, J., Kelly, A., Austin, P., Carson, S., Meunier, H., So, A., Erlich, H., Spielman, R., Bodmer, J., and Bodmer, W. F.: Structure, sequence and polymorphism in the HLA-D region. Immunol. Rev. 85: 5–43, 1985
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
Weiss, E., Golden, L., Zakut, R., Mellor, A., Fahrner, K., Kvist, S., and Flavell, R. A.: The DNA sequence of the H-2Kb gene: Evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibility antigens. EMBO J. 2: 453–462, 1983
Widera, G. and Flavell, R. A.: The nucleotide sequence of the murine I-Eβ b immune response gene—evidence for gene conversion events in class II genes of the major histocompatibility complex. EMBO J. 3: 1221–1225, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Meunier, H.F., Carson, S., Bodmer, W.F. et al. An isolated β 1 exon next to the DR α gene in the HLA-D region. Immunogenetics 23, 172–180 (1986). https://doi.org/10.1007/BF00373818
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00373818