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. 1984 Apr;3(4):869–872. doi: 10.1002/j.1460-2075.1984.tb01898.x

The complete sequence of the mRNA for the HLA-DR-associated invariant chain reveals a polypeptide with an unusual transmembrane polarity.

M Strubin, B Mach, E O Long
PMCID: PMC557440  PMID: 6586420

Abstract

A non-polymorphic polypeptide is associated intracellularly with the alpha and beta chains of murine Ia antigens and of human HLA-DR antigens. The exact role and the structure of this invariant chain have not been determined so far. A cDNA clone encoding the 33 000 dalton human invariant chain has been isolated. The nucleotide sequence of a near full-length cDNA clone, together with the sequence of the 5' portion of the mRNA determined by primer-extension, are reported here. The protein structure deduced from that sequence shows an unusual feature: the presence of a hydrophobic transmembrane region near the NH2 terminus, and of two glycosylation sites near the middle, indicates that the invariant chain has a polarity of membrane insertion which is inverted relative to histocompatibility antigens and most transmembrane proteins.

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Selected References

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  1. Bretscher M. S. Membrane structure: some general principles. Science. 1973 Aug 17;181(4100):622–629. doi: 10.1126/science.181.4100.622. [DOI] [PubMed] [Google Scholar]
  2. Charron D. J., Aellen-Schulz M. F., St Geme J., 3rd, Erlich H. A., McDevitt H. O. Biochemical characterization of an invariant polypeptide associated with Ia antigens in human and mouse. Mol Immunol. 1983 Jan;20(1):21–32. doi: 10.1016/0161-5890(83)90101-3. [DOI] [PubMed] [Google Scholar]
  3. Charron D. J., McDevitt H. O. Analysis of HLA-D region-associated molecules with monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6567–6571. doi: 10.1073/pnas.76.12.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Claesson L., Peterson P. A. Association of human gamma chain with class II transplantation antigens during intracellular transport. Biochemistry. 1983 Jun 21;22(13):3206–3213. doi: 10.1021/bi00282a026. [DOI] [PubMed] [Google Scholar]
  5. Day C. E., Jones P. P. The gene encoding the Ia antigen-associated invariant chain (Ii) is not linked to the H-2 complex. Nature. 1983 Mar 10;302(5904):157–159. doi: 10.1038/302157a0. [DOI] [PubMed] [Google Scholar]
  6. Drickamer K. Complete amino acid sequence of a membrane receptor for glycoproteins. Sequence of the chicken hepatic lectin. J Biol Chem. 1981 Jun 10;256(11):5827–5839. [PubMed] [Google Scholar]
  7. Fields S., Winter G., Brownlee G. G. Structure of the neuraminidase gene in human influenza virus A/PR/8/34. Nature. 1981 Mar 19;290(5803):213–217. doi: 10.1038/290213a0. [DOI] [PubMed] [Google Scholar]
  8. Frank G., Brunner J., Hauser H., Wacker H., Semenza G., Zuber H. The hydrophobic anchor of small-intestinal sucrase--isomaltase: N-terminal sequence of isomaltase subunit. FEBS Lett. 1978 Dec 1;96(1):183–188. doi: 10.1016/0014-5793(78)81090-4. [DOI] [PubMed] [Google Scholar]
  9. Ghosh P. K., Reddy V. B., Piatak M., Lebowitz P., Weissman S. M. Determination of RNA sequences by primer directed synthesis and sequencing of their cDNA transcripts. Methods Enzymol. 1980;65(1):580–595. doi: 10.1016/s0076-6879(80)65061-7. [DOI] [PubMed] [Google Scholar]
  10. Giorgi C., Blumberg B. M., Kolakofsky D. Sendai virus contains overlapping genes expressed from a single mRNA. Cell. 1983 Dec;35(3 Pt 2):829–836. doi: 10.1016/0092-8674(83)90115-0. [DOI] [PubMed] [Google Scholar]
  11. Jones P. P., Murphy D. B., Hewgill D., McDevitt H. O. Detection of a common polypeptide chain in I--A and I--E sub-region immunoprecipitates. Mol Immunol. 1979 Jan;16(1):51–60. doi: 10.1016/0161-5890(79)90027-0. [DOI] [PubMed] [Google Scholar]
  12. Klein J., Juretic A., Baxevanis C. N., Nagy Z. A. The traditional and a new version of the mouse H-2 complex. Nature. 1981 Jun 11;291(5815):455–460. doi: 10.1038/291455a0. [DOI] [PubMed] [Google Scholar]
  13. Koch N., Harris A. W. Differential expression of the invariant chain in mouse tumor cells: relationship to B lymphoid development. J Immunol. 1984 Jan;132(1):12–15. [PubMed] [Google Scholar]
  14. Koch N., Hämmerling G. J., Szymura J., Wabl M. R. Ia associated Ii chain is not encoded by chromosome 17 of the mouse. Immunogenetics. 1982;16(6):603–606. doi: 10.1007/BF00372029. [DOI] [PubMed] [Google Scholar]
  15. Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. doi: 10.1128/mr.47.1.1-45.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Lee J. S., Trowsdale J., Bodmer W. F. cDNA clones coding for the heavy chain of human HLA-DR antigen. Proc Natl Acad Sci U S A. 1982 Jan;79(2):545–549. doi: 10.1073/pnas.79.2.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Long E. O., Strubin M., Wake C. T., Gross N., Carrel S., Goodfellow P., Accolla R. S., Mach B. Isolation of cDNA clones for the p33 invariant chain associated with HLA-DR antigens. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5714–5718. doi: 10.1073/pnas.80.18.5714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Long E. O., Wake C. T., Gorski J., Mach B. Complete sequence of an HLA-dR beta chain deduced from a cDNA clone and identification of multiple non-allelic DR beta chain genes. EMBO J. 1983;2(3):389–394. doi: 10.1002/j.1460-2075.1983.tb01435.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Long E. O., Wake C. T., Strubin M., Gross N., Accolla R. S., Carrel S., Mach B. Isolation of distinct cDNA clones encoding HLA-DR beta chains by use of an expression assay. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7465–7469. doi: 10.1073/pnas.79.23.7465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Machamer C. E., Cresswell P. Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens. J Immunol. 1982 Dec;129(6):2564–2569. [PubMed] [Google Scholar]
  22. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  23. McMillan M., Frelinger J. A., Jones P. P., Murphy D. B., McDevitt H. O., Hood L. Structure of murine Ia antigens. Two dimensional electrophoretic analyses and high pressure liquid chromatography tryptic peptide maps of products of the I-A and I-E subregions and of an associated invariant polypeptide. J Exp Med. 1981 Apr 1;153(4):936–950. doi: 10.1084/jem.153.4.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Owen M. J., Kissonerghis A. M., Lodish H. F., Crumpton M. J. Biosynthesis and maturation of HLA-DR antigens in vivo. J Biol Chem. 1981 Sep 10;256(17):8987–8993. [PubMed] [Google Scholar]
  25. Rabourdin-Combe C., Mach B. Expression of HLA-DR antigens at the surface of mouse L cells co-transfected with cloned human genes. Nature. 1983 Jun 23;303(5919):670–674. doi: 10.1038/303670a0. [DOI] [PubMed] [Google Scholar]
  26. Sabatini D. D., Kreibich G., Morimoto T., Adesnik M. Mechanisms for the incorporation of proteins in membranes and organelles. J Cell Biol. 1982 Jan;92(1):1–22. doi: 10.1083/jcb.92.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  28. Shackelford D. A., Kaufman J. F., Korman A. J., Strominger J. L. HLA-DR antigens: structure, separation of subpopulations, gene cloning and function. Immunol Rev. 1982;66:133–187. doi: 10.1111/j.1600-065x.1982.tb00437.x. [DOI] [PubMed] [Google Scholar]
  29. Shackelford D. A., Strominger J. L. Demonstration of structural polymorphism among HLA-DR light chains by two-dimensional gel electrophoresis. J Exp Med. 1980 Jan 1;151(1):144–165. doi: 10.1084/jem.151.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steck T. L. The band 3 protein of the human red cell membrane: a review. J Supramol Struct. 1978;8(3):311–324. doi: 10.1002/jss.400080309. [DOI] [PubMed] [Google Scholar]
  31. Wake C. T., Long E. O., Strubin M., Gross N., Accolla R., Carrel S., Mach B. Isolation of cDNA clones encoding HLA-DR alpha chains. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6979–6983. doi: 10.1073/pnas.79.22.6979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. von Heijne G. Membrane proteins: the amino acid composition of membrane-penetrating segments. Eur J Biochem. 1981 Nov;120(2):275–278. doi: 10.1111/j.1432-1033.1981.tb05700.x. [DOI] [PubMed] [Google Scholar]

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