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. 1984 Jul 1;99(1 Pt 1):226–232. doi: 10.1083/jcb.99.1.226

Beta 2-microglobulin induces intracellular transport of human class I transplantation antigen heavy chains in Xenopus laevis oocytes

PMCID: PMC2275618  PMID: 6429156

Abstract

Human class I transplantation antigens are cell-surface-expressed molecules composed of one glycosylated, membrane-integrated heavy chain and one nonglycosylated, water-soluble subunit, beta 2-microglobulin (beta 2m). We have examined the intracellular transport of the two subunits by microinjecting mRNA into Xenopus laevis oocytes. Beta 2m, translated in oocytes, was transported and secreted into the medium in the absence of heavy chains whereas heavy chains were retained in the endoplasmic reticulum if not cotranslated with beta 2m. In the presence of beta 2m, heavy chains resisted digestion by endoglycosidase H (Endo H), suggesting that beta 2m promotes the transport of heavy chains from endoplasmic reticulum to the Golgi compartment. Pulse-chase experiments confirmed this notion. The possibility that heavy chains aggregate irreversibly when synthesized in the absence of beta 2m was ruled out and it is demonstrated that performed heavy chains will become transported once beta 2m is available. It is suggested that intracellular transport is controlled by structural features that are part of the transported polypeptide. If so, beta 2m but not heavy chains may possess such features.

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Selected References

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  1. Arce-Gomez B., Jones E. A., Barnstable C. J., Solomon E., Bodmer W. F. The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin. Tissue Antigens. 1978 Feb;11(2):96–112. doi: 10.1111/j.1399-0039.1978.tb01233.x. [DOI] [PubMed] [Google Scholar]
  2. Beyer T. A., Rearick J. I., Paulson J. C., Prieels J. P., Sadler J. E., Hill R. L. Biosynthesis of mammalian glycoproteins. Glycosylation pathways in the synthesis of the nonreducing terminal sequences. J Biol Chem. 1979 Dec 25;254(24):12531–12534. [PubMed] [Google Scholar]
  3. Blobel G., Dobberstein B. Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol. 1975 Dec;67(3):835–851. doi: 10.1083/jcb.67.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blobel G. Intracellular protein topogenesis. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496–1500. doi: 10.1073/pnas.77.3.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bochner B. R., Huang H. C., Schieven G. L., Ames B. N. Positive selection for loss of tetracycline resistance. J Bacteriol. 1980 Aug;143(2):926–933. doi: 10.1128/jb.143.2.926-933.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  7. Croce C. M., Linnenbach A., Huebner K., Parnes J. R., Margulies D. H., Appella E., Seidman J. G. Control of expression of histocompatibility antigens (H-2) and beta 2-microglobulin in F9 teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5754–5758. doi: 10.1073/pnas.78.9.5754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dobberstein B., Garoff H., Warren G., Robinson P. J. Cell-free synthesis and membrane insertion of mouse H-2Dd histocompatibility antigen and beta 2-microglobulin. Cell. 1979 Aug;17(4):759–769. doi: 10.1016/0092-8674(79)90316-7. [DOI] [PubMed] [Google Scholar]
  9. Fries E., Gustafsson L., Peterson P. A. Four secretory proteins synthesized by hepatocytes are transported from endoplasmic reticulum to Golgi complex at different rates. EMBO J. 1984 Jan;3(1):147–152. doi: 10.1002/j.1460-2075.1984.tb01775.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gurdon J. B. Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal. J Embryol Exp Morphol. 1976 Dec;36(3):523–540. [PubMed] [Google Scholar]
  11. Hall M. N., Schwartz M., Silhavy T. J. Sequence information within the lamB genes in required for proper routing of the bacteriophage lambda receptor protein to the outer membrane of Escherichia coli K-12. J Mol Biol. 1982 Mar 25;156(1):93–112. doi: 10.1016/0022-2836(82)90461-2. [DOI] [PubMed] [Google Scholar]
  12. Hayman M. J., Crumpton M. J. Isolation of glycoproteins from pig lymphocyte plasma membrane using Lens culinaris phytohemagglutinin. Biochem Biophys Res Commun. 1972 May 26;47(4):923–930. doi: 10.1016/0006-291x(72)90581-5. [DOI] [PubMed] [Google Scholar]
  13. Hunt L. A., Etchison J. R., Summers D. F. Oligosaccharide chains are trimmed during synthesis of the envelope glycoprotein of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1978 Feb;75(2):754–758. doi: 10.1073/pnas.75.2.754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kvist S., Peterson P. A. Isolation and partial characterization of a beta2-microglobulin-containing, H-2 antigen-like murine serum protein. Biochemistry. 1978 Oct 31;17(22):4794–4801. doi: 10.1021/bi00615a029. [DOI] [PubMed] [Google Scholar]
  15. Kvist S., Wiman K., Claesson L., Peterson P. A., Dobberstein B. Membrane insertion and oligomeric assembly of HLA-DR histocompatibility antigens. Cell. 1982 May;29(1):61–69. doi: 10.1016/0092-8674(82)90090-3. [DOI] [PubMed] [Google Scholar]
  16. Kämpe O., Bellgrau D., Hammerling U., Lind P., Päbo S., Severinsson L., Peterson P. A. Complex formation of class I transplantation antigens and a viral glycoprotein. J Biol Chem. 1983 Sep 10;258(17):10594–10598. [PubMed] [Google Scholar]
  17. Lodish H. F., Kong N., Snider M., Strous G. J. Hepatoma secretory proteins migrate from rough endoplasmic reticulum to Golgi at characteristic rates. Nature. 1983 Jul 7;304(5921):80–83. doi: 10.1038/304080a0. [DOI] [PubMed] [Google Scholar]
  18. Mains P. E., Sibley C. H. The requirement of light chain for the surface deposition of the heavy chain of immunoglobulin M. J Biol Chem. 1983 Apr 25;258(8):5027–5033. [PubMed] [Google Scholar]
  19. Nilsson K., Evrin P. E., Welsh K. I. Production of beta 2-microglobulin by normal and malignant human cell lines and peripheral lymphocytes. Transplant Rev. 1974;21(0):53–84. doi: 10.1111/j.1600-065x.1974.tb01546.x. [DOI] [PubMed] [Google Scholar]
  20. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  21. Ostberg L., Rask L., Nilsson K., Peterson P. A. Independent expression of the two HL-A antigen polypeptide chains. Eur J Immunol. 1976 Jul;5(7):462–468. doi: 10.1002/eji.1830050707. [DOI] [PubMed] [Google Scholar]
  22. Owen M. J., Kissonerghis A. M., Lodish H. F. Biosynthesis of HLA-A and HLA-B antigens in vivo. J Biol Chem. 1980 Oct 25;255(20):9678–9684. [PubMed] [Google Scholar]
  23. Parham P., Alpert B. N., Orr H. T., Strominger J. L. Carbohydrate moiety of HLA antigens. Antigenic properties and amino acid sequences around the site of glycosylation. J Biol Chem. 1977 Nov 10;252(21):7555–7567. [PubMed] [Google Scholar]
  24. Ploegh H. L., Cannon L. E., Strominger J. L. Cell-free translation of the mRNAs for the heavy and light chains of HLA-A and HLA-B antigens. Proc Natl Acad Sci U S A. 1979 May;76(5):2273–2277. doi: 10.1073/pnas.76.5.2273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ploegh H. L., Orr H. T., Strominger J. L. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell. 1981 May;24(2):287–299. doi: 10.1016/0092-8674(81)90318-4. [DOI] [PubMed] [Google Scholar]
  26. Rask L., Lindblom J. B., Peterson P. A. Structural and immunological similarities between HLA antigens from three loci. Eur J Immunol. 1976 Feb;6(2):93–100. doi: 10.1002/eji.1830060205. [DOI] [PubMed] [Google Scholar]
  27. Ricciardi R. P., Miller J. S., Roberts B. E. Purification and mapping of specific mRNAs by hybridization-selection and cell-free translation. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4927–4931. doi: 10.1073/pnas.76.10.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosa F., Berissi H., Weissenbach J., Maroteaux L., Fellous M., Revel M. The beta2-microglobulin mRNA in human Daudi cells has a mutated initiation codon but is still inducible by interferon. EMBO J. 1983;2(2):239–243. doi: 10.1002/j.1460-2075.1983.tb01412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sege K., Rask L., Peterson P. A. Role of beta2-microglobulin in the intracellular processing of HLA antigens. Biochemistry. 1981 Aug 4;20(16):4523–4530. doi: 10.1021/bi00519a003. [DOI] [PubMed] [Google Scholar]
  30. Tarentino A. L., Maley F. Purification and properties of an endo-beta-N-acetylglucosaminidase from Streptomyces griseus. J Biol Chem. 1974 Feb 10;249(3):811–817. [PubMed] [Google Scholar]
  31. Trägårdh L., Curman B., Wiman K., Rask L., Peterson P. A. Chemical, physical-chemical, and immunological properties of papain-solubilized human transplatation antigens. Biochemistry. 1979 May 29;18(11):2218–2226. doi: 10.1021/bi00578a013. [DOI] [PubMed] [Google Scholar]
  32. Webb C. G., Gall W. E., Edelman G. M. Synthesis and distribution of H-2 antigens in preimplantation mouse embryos. J Exp Med. 1977 Oct 1;146(4):923–932. doi: 10.1084/jem.146.4.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wiman K., Larhammar D., Claesson L., Gustafsson K., Schenning L., Bill P., Böhme J., Denaro M., Dobberstein B., Hammerling U. Isolation and identification of a cDNA clone corresponding to an HLA-DR antigen beta chain. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1703–1707. doi: 10.1073/pnas.79.6.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu G. E., Hozumi N., Murialdo H. Secretion of a lambda 2 immunoglobulin chain is prevented by a single amino acid substitution in its variable region. Cell. 1983 May;33(1):77–83. doi: 10.1016/0092-8674(83)90336-7. [DOI] [PubMed] [Google Scholar]
  35. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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