Immunogenetics

, Volume 27, Issue 6, pp 449–455

MHC class II sequences of an HLA-DR2 narcoleptic

  • C. B. Lock
  • A. K. L. So
  • K. I. Welsh
  • J. D. Parkes
  • J. Trowsdale
Original Articles

Abstract

Narcolepsy has a 98% association with the DR2-Dw2/DQw1 haplotype. To establish if a disease-specific allele is present in narcolepsy, a cDNA library was made from a B-cell line from a DR2,4/DQw1,3 narcoleptic. Clones encoding the two expressed DR2β chains, along with DQw1 α and β chains, were isolated and completely sequenced. The coding regions of these four genes were similar to published nucleotide and protein sequences from corresponding healthy controls, with some minor exceptions. The 3′ untranslated region of one of the DR2β genes in the narcoleptic was extended by 42 bp. Complete sequences were not available for DQw1.2 α or β from healthy individuals, but first domain nucleotide sequences showed only a single nonproductive difference in DQα. Partial protein sequences of both DQ α and β from published data were identical. Although the effects of minor differences cannot be ruled out completely, it is concluded that there are probably no narcolepsy-specific DRβ or DQ α/β sequences, and that the alleles found in narcolepsy are representative of those found in the healthy population.

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References

  1. Andersson, G., Larhammar, D., Widmark, E., Servenius, B., Peterson, P. A., and Rask, L.: Class II genes of the human major histocompatibility complex; organisation and evolutionary relationship of the DR β genes. J. Biol. Chem. 262: 8748–8758, 1987Google Scholar
  2. Andreas-Zeitz, A., Keller, E., and Scholz, S.: DR2-negative narcolepsy. Lancet 2: 684–685, 1986Google Scholar
  3. Andreas-Zeitz, A., Keller, E., and Roth, B.: The occurrence of HLA-DR2 in 118 narcoleptics. (Abstract.) Fifth International Congress of Sleep Research, Copenhagen, Denmark, June 28–July 3, 1987Google Scholar
  4. Angellini, G., DePreval, C., Gorski, J., and Mach, B.: High resolution analysis of the human HLA-DR polymorphism by hybridisation with sequence-specific oligonucleotide probes. Proc. Natl. Acad. Sci. U.S.A. 83: 4489–4493, 1986Google Scholar
  5. Auffray, C., Lillie, J. W., Arnot, D., Grossberger, D., Kappes, D., and Strominger, J. L.: Isotypic and allotypic variation of human class II histocompatibility antigen α-chain genes. Nature 308: 327–333, 1984Google Scholar
  6. Batchelor, J. R., Hors, J., Dodi, I. A., Betuel, H., and Borelli, I.: Antigen report: HLA-DR2. In E. D. Albert, M. P. Baur, and W. R. Mayr (eds.): Histocompatibility Testing 1984, pp. 186–187, Springer-Verlag, Berlin, 1984Google Scholar
  7. Bell, J. I., Estess, P., St. John, T., Saiki, R., Watling, D. L., Erlich, H. A., and McDevitt, H. O.: DNA sequence and characterisation of human class II major histocompatibility complex β chain from the DR1 haplotype. Proc. Natl. Acad. Sci. U.S.A. 82: 3405–3409, 1985Google Scholar
  8. Bell, J. I., Denney, D., Foster, L., Belt, T., and McDevitt, H. O.: Allelic variation in the DR subregion of the human major histocompatibility complex. Proc. Natl. Acad. Sci. U.S.A. 84: 6234–6238, 1987Google Scholar
  9. Billiard, M. and Seignalet, J.: Extraordinary association between HLA-DR2 and narcolepsy. Lancet 1: 226–227, 1985Google Scholar
  10. Confavreux, C., Gebuhrer, L., Betuel, H., Friedel, C., Bastuji, H., Aimard, G., Devic, M., and Jouvet, M.: HLA-DR2 negative narcolepsy. J. Neurol. Neurosurg. Psychiatry 50: 635–636, 1987Google Scholar
  11. Feinberg, A. and Vogelstein, B.: A technique for radiolabelling DNA restriction endonuclease fragments to a high specific activity. Anal. Biochem. 132: 6–13, 1984Google Scholar
  12. Gubler, V. and Hoffman, B. J.: A single and very efficient method for generating cDNA libraries. Gene 25: 263–269, 1983Google Scholar
  13. Guilleminault, C.: HLA-DR2 and narcolepsy: not all narcolepticcataplectic patients are DR2. Hum. Immunol. 17: 1–2, 1986Google Scholar
  14. Holloman, J. D., Bell, J. L., and Lee, T.: Major histocompatibility complex restriction fragment length polymorphism in narcolepsy. (Abstract.) Second International Symposium on Narcolepsy, Stanford, California, July 6–7, 1985Google Scholar
  15. Honda, Y., Doi, Y., Juji, T., and Satake, M.: Narcolepsy and HLApositive DR2 as a prerequisite for the development of narcolepsy. Folia Psychiatr. Neural. Jpn 38: 360, 1984Google Scholar
  16. Inoko, H., Ando, A., Tsuji, K., Matsuki, K., Juji, T., and Honda, Y.: HLA-DQ β chain DNA restriction fragments can differentiate between healthy and narcoleptic individuals with HLA-DR2. Immunogenetics 23: 126–128, 1986Google Scholar
  17. Juji, T., Satake, M., Honda, Y., and Doi, Y.: HLA antigens in Japanese patients with narcolepsy. Tissue Antigens 24: 316–319, 1984Google Scholar
  18. Juji, T., Matsuki, K., Naohara, T., Satake, M., and Honda, Y.: HLA antigens in Japanese patients with narcolepsy. Lancet 1: 227, 1985Google Scholar
  19. Kaufman, J. F., Auffray, C., Korman, A. J., Shackelford, D. A., and Strominger, J.: The class II molecules of the human and murine major histocompatibility complex. Cell 36: 1–13, 1984Google Scholar
  20. Klein, J.: The Natural History of the Major Histocompatibility Complex, John Wiley and Sons, Chichester, 1987Google Scholar
  21. Kratzin, H., Gotz, H., Thinnes, F. P., Kruse, T., Barnikol, H. U., Wernet, P., and Hilschmann, N.: Structure of human class II antigens expressed by a homozygous lymphoblastoid B-cell line. In B. G. Solheim, E. Moller, and S. Ferrone (eds.): HLA Class II Antigens, pp. 49–70, Springer-Verlag, New York, 1986Google Scholar
  22. Langdon, N., Welsh, K. I., Van Dam, M., Vaughan, R. W., and Parkes, J. D.: Genetic markers in narcolepsy. Lancet 2: 1178–1180, 1984Google Scholar
  23. Langdon, N., Lock, C., Welsh, K., Vergani, D., Dorow, R., Wachtez, H., Palenschat, D., and Parkes, J. D.: Immune factors in narcolepsy. Sleep 9: 143–148, 1986Google Scholar
  24. Larhammar, D., Hyldig-Nielsen, J. J., Servenius, B., Andersson, G., Rask, L., and Peterson, P.: Exon-intron organization and complete nucleotide sequence of a major histocompatibility antigen DCβ gene. Proc. Natl. Acad. Sci. U.S.A. 80: 7313–7317, 1983Google Scholar
  25. Lavie, P., Peled, R., Brautbar, C., Friedmann, A., Steinman, L, and Wilner, A.: Narcolepsy in Israeli Jewish patients is associated with the HLA DR2 Dw2 haplotype. (Abstract.) Fifth International Congress of Sleep Research, Copenhagen, Denmark, June 28–July 3, 1987Google Scholar
  26. Lee, B. S. M., Rust, N. A., McMichael, A. J., and McDevitt, H. O.: HLA-DR2 subtypes form an additional supertypic family of DR β alleles. Proc. Natl. Acad. Sci. U.S.A. 84: 4591–4595, 1987aGoogle Scholar
  27. Lee, B. S. M., Bell, J. L., Rust, N. A., and McDevitt, H. O.: Structural and functional variability among DQβ alleles of DR2 subtypes. Immunogenetics 26: 85–91, 1987bGoogle Scholar
  28. Lock, C. B., Parkes, J. D., Welsh, K. I., and So, A.: Narcolepsy and immunity. In P. Behan (ed.): Neuroimmunology, chapter 31, Blackwell Scientific Publications, Oxford, Boston, 1987Google Scholar
  29. Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1982Google Scholar
  30. Marcadet, A., Gebuhrer, L., Betuel, H., Seignalet, J., Freidel, A. C., Confavreux, C., Billiard, M., Dausset, J., and Cohen, D.: DNA polymorphism related to HLA-DR2 Dw2 in patients with narcolepsy. Immunogenetics 22: 679–683, 1986Google Scholar
  31. Mitler, M. M., Shafor, R., Sobers, M., Hajdukovich, R. M., and Rubin, R. L.: Human leucocyte antigen (HLA) studies in excessive somnolence: narcolepsy versus sleep apnea. Sleep Res. 9: 148, 1986Google Scholar
  32. Natali, P. G., DeMartino, C., Quaranta, V., Nicotra, M. R., Frezza, F., Pellegrino, M. A., and Ferrone, S.: Expression of Ia-like antigens in normal human nonlymphoid tissues. Transplantation 31: 75–78, 1981Google Scholar
  33. Othman, J., Rundell, O. H., and Orr, W. C.: Not all narcoleptics are HLA-DR2 positive. (Abstract.) Fifth International Congress of Sleep Research, Copenhagen, Denmark, June 28–July 3, 1987Google Scholar
  34. Poirier, G., Montplaisir, J., Lebrun, A., and Decary, F.: HLA antigens in narcolepsy. (Abstract.) Second International Symposium on Narcolepsy, Stanford, California, July 6–7, 1985Google Scholar
  35. Thein, S. L. and Wallace, B.: The use of synthetic oligonucleotides as specific hybridization probes in the diagnosis of genetic disorders. In K. E. Davies (ed.): Human Genetic Diseases: A Practical Approach, IRL Press Ltd., Oxford, pp. 33–50, 1986Google Scholar
  36. Tiwari, J. L. and Terasaki, P. L.: HLA and Disease Associations, Springer-Verlag, New York, 1985Google Scholar
  37. Todd, J. A., Bell, J. L., and McDevitt, H. O.: HLA-DQ β gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329: 599–604, 1987Google Scholar
  38. Tonnelle, C., DeMars, R., and Long, E. O.: DO β: a new β chain gene in HLA-D with a distinct regulation of expression. EMBO J. 4: 2839–2847, 1985Google Scholar
  39. Trowsdale, J., Lee, J., and Carey, J.: Sequences related to HLA-DR α chain on human chromosome 6: restriction enzyme polymorphism detected with DC α chain probes. Proc. Natl. Acad. Sci. U.S.A. 80: 1983Google Scholar
  40. Tsukamoto, K., Yasunami, M., Kimura, A., Inoko, H., Ando, A., Hirose, T., Inayama, S., and Sasazuki, T.: DQw1 β gene from HLA-DR2-Dw12 consists of six exons and expresses multiple DQw1β polypeptides through alternative splicing. Immunogenetics 25: 343–346, 1987Google Scholar
  41. Turco, E., Care, A., Compagnone-Post, P., Robinson, C., Cascino, I., and Trucco, M.: Allelic forms of the alpha- and beta-chain genes encoding DQwl-positive heterodimers. Immunogenetics 26: 282–290, 1987Google Scholar
  42. Watson, C. T. and Jackson, J. F.: An alternative procedure for the synthesis of double-stranded cDNA for cloning in phage and plasmid vectors. In D. M. Glover (ed.): DNA Cloning, Volume I, pp. 79–88, IRL Press, Oxford, 1985Google Scholar
  43. Wu, S., Saunders, T. L., and Bach, F. H.: Polymorphism of human la antigens generated by reciprocal intergenic exchange between two DR β loci. Nature 324: 676–679, 1986Google Scholar
  44. Wu, S., Yabe, T., Madden, M., Saunders, T. L., and Bach, F. H.: cDNA cloning and sequencing reveals that the electrophoretically constant DRβ2 molecules, as well as the variable DRβ1 molecules, from HLA-DR2 subtypes have different amino acid sequences including a hypervariable region for a functionally important epitope. J. Immunol. 138: 2953–2959, 1987Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • C. B. Lock
    • 1
  • A. K. L. So
    • 2
  • K. I. Welsh
    • 3
  • J. D. Parkes
    • 1
  • J. Trowsdale
    • 2
  1. 1.Department of Neurology, King's College Hospital School of MedicineDentistry, and Institute of PsychiatryDenmark Hill, LondonUK
  2. 2.Human Immunogenetics LaboratoryImperial Cancer Research FundLincoln's Inn Fields, LondonUK
  3. 3.Tissue Typing, Guy's HospitalLondonUK
  4. 4.Royal Postgraduate Medical SchoolHammersmith HospitalLondonUK

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