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J Cell Biol. 1991 March 2; 112(6): 1099–1115.
PMCID: PMC2288894

Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules

Abstract

Chemical cross-linking and gel permeation chromatography were used to examine early events in the biogenesis of class I histocompatibility molecules. We show that newly synthesized class I heavy chains associate rapidly and quantitatively with an 88-kD protein in three murine tumor cell lines. This protein (p88) does not appear to possess Asn-linked glycans and it is not the abundant ER protein, GRP94. The class I-p88 complex exists transiently (t1/2 = 20-45 min depending on the specific class I heavy chain) and several lines of evidence suggest that p88 dissociates from the complex while still in the ER. Dissociation is not triggered upon binding of beta 2-microglobulin to the heavy chain (t1/2 = 2-5 min). However, the rate of dissociation does correlate with the characteristic rate of ER to Golgi transport for the particular class I molecule studied. Consequently, dissociation of p88 may be rate limiting for ER to Golgi transport. Class I molecules bind antigenic peptides, apparently in the ER, for subsequent presentation to cytotoxic T lymphocytes at the cell surface. p88 could promote peptide binding or it may retain class I molecules in the ER during formation of the ternary complex of heavy chain, beta 2- microglobulin, and peptide.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Allen H, Fraser J, Flyer D, Calvin S, Flavell R. Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7447–7451. [PubMed]
  • Balch WE, Elliott MM, Keller DS. ATP-coupled transport of vesicular stomatitis virus G protein between the endoplasmic reticulum and the Golgi. J Biol Chem. 1986 Nov 5;261(31):14681–14689. [PubMed]
  • Beck JC, Hansen TH, Cullen SE, Lee DR. Slower processing, weaker beta 2-M association, and lower surface expression of H-2Ld are influenced by its amino terminus. J Immunol. 1986 Aug 1;137(3):916–923. [PubMed]
  • Brenner MB, McLean J, Scheft H, Riberdy J, Ang SL, Seidman JG, Devlin P, Krangel MS. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. [PubMed]
  • Cerundolo V, Alexander J, Anderson K, Lamb C, Cresswell P, McMichael A, Gotch F, Townsend A. Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature. 1990 May 31;345(6274):449–452. [PubMed]
  • Copeland CS, Doms RW, Bolzau EM, Webster RG, Helenius A. Assembly of influenza hemagglutinin trimers and its role in intracellular transport. J Cell Biol. 1986 Oct;103(4):1179–1191. [PMC free article] [PubMed]
  • Copeland CS, Zimmer KP, Wagner KR, Healey GA, Mellman I, Helenius A. Folding, trimerization, and transport are sequential events in the biogenesis of influenza virus hemagglutinin. Cell. 1988 Apr 22;53(2):197–209. [PubMed]
  • Degen E, Laferté S, Elliott BE, Williams DB. Different class I antigen oligosaccharides on a murine tumor and a lectin-resistant variant are not responsible for the differential recognition of the tumors by CTL. Int J Cancer. 1989 May 15;43(5):828–836. [PubMed]
  • Doms RW, Keller DS, Helenius A, Balch WE. Role for adenosine triphosphate in regulating the assembly and transport of vesicular stomatitis virus G protein trimers. J Cell Biol. 1987 Nov;105(5):1957–1969. [PMC free article] [PubMed]
  • Doms RW, Ruusala A, Machamer C, Helenius J, Helenius A, Rose JK. Differential effects of mutations in three domains on folding, quaternary structure, and intracellular transport of vesicular stomatitis virus G protein. J Cell Biol. 1988 Jul;107(1):89–99. [PMC free article] [PubMed]
  • Doms RW, Russ G, Yewdell JW. Brefeldin A redistributes resident and itinerant Golgi proteins to the endoplasmic reticulum. J Cell Biol. 1989 Jul;109(1):61–72. [PMC free article] [PubMed]
  • Dorner AJ, Bole DG, Kaufman RJ. The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. J Cell Biol. 1987 Dec;105(6 Pt 1):2665–2674. [PMC free article] [PubMed]
  • Dunphy WG, Brands R, Rothman JE. Attachment of terminal N-acetylglucosamine to asparagine-linked oligosaccharides occurs in central cisternae of the Golgi stack. Cell. 1985 Feb;40(2):463–472. [PubMed]
  • Ellis J. Proteins as molecular chaperones. Nature. 328(6129):378–379. [PubMed]
  • Evans GA, Margulies DH, Shykind B, Seidman JG, Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. [PubMed]
  • Fujiwara T, Oda K, Yokota S, Takatsuki A, Ikehara Y. Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum. J Biol Chem. 1988 Dec 5;263(34):18545–18552. [PubMed]
  • Germain RN. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. [PubMed]
  • Gerhard W, Yewdell J, Frankel ME, Webster R. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature. 1981 Apr 23;290(5808):713–717. [PubMed]
  • Gething MJ, McCammon K, Sambrook J. Expression of wild-type and mutant forms of influenza hemagglutinin: the role of folding in intracellular transport. Cell. 1986 Sep 12;46(6):939–950. [PubMed]
  • GORER PA. Studies in antibody response of mice to tumour inoculation. Br J Cancer. 1950 Dec;4(4):372–379. [PMC free article] [PubMed]
  • Hämmerling GJ, Rüsch E, Tada N, Kimura S, Hämmerling U. Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4737–4741. [PubMed]
  • Hemler ME, Huang C, Takada Y, Schwarz L, Strominger JL, Clabby ML. Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem. 1987 Aug 25;262(24):11478–11485. [PubMed]
  • Herrmann SH, Mescher MF. Purification of the H-2Kk molecule of the murine major histocompatibility complex. J Biol Chem. 1979 Sep 25;254(18):8713–8716. [PubMed]
  • Hiebert SW, Lamb RA. Cell surface expression of glycosylated, nonglycosylated, and truncated forms of a cytoplasmic protein pyruvate kinase. J Cell Biol. 1988 Sep;107(3):865–876. [PMC free article] [PubMed]
  • Hosken NA, Bevan MJ. Defective presentation of endogenous antigen by a cell line expressing class I molecules. Science. 1990 Apr 20;248(4953):367–370. [PubMed]
  • Hurtley SM, Bole DG, Hoover-Litty H, Helenius A, Copeland CS. Interactions of misfolded influenza virus hemagglutinin with binding protein (BiP). J Cell Biol. 1989 Jun;108(6):2117–2126. [PMC free article] [PubMed]
  • Kimball ES, Coligan JE. Structure of class I major histocompatibility antigens. Contemp Top Mol Immunol. 1983;9:1–63. [PubMed]
  • Krangel MS, Orr HT, Strominger JL. Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell. 1979 Dec;18(4):979–991. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Lagarde AE, Donaghue TP, Kerbel R, Siminovitch L. Metastatic properties of distinct phenotypic classes of lectin-resistant mutants isolated from murine MDAY-D2 cell line. Somat Cell Mol Genet. 1984 Sep;10(5):503–519. [PubMed]
  • Lancet D, Parham P, Strominger JL. Heavy chain of HLA-A and HLA-B antigens is conformationally labile: a possible role for beta 2-microglobulin. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3844–3848. [PubMed]
  • Lippincott-Schwartz J, Donaldson JG, Schweizer A, Berger EG, Hauri HP, Yuan LC, Klausner RD. Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway. Cell. 1990 Mar 9;60(5):821–836. [PubMed]
  • Ljunggren HG, Päbo S, Cochet M, Kling G, Kourilsky P, Kärre K. Molecular analysis of H-2-deficient lymphoma lines. Distinct defects in biosynthesis and association of MHC class I heavy chains and beta 2-microglobulin observed in cells with increased sensitivity to NK cell lysis. J Immunol. 1989 Apr 15;142(8):2911–2917. [PubMed]
  • Long EO, Jacobson S. Pathways of viral antigen processing and presentation to CTL: defined by the mode of virus entry? Immunol Today. 1989 Feb;10(2):45–48. [PubMed]
  • Machamer CE, Rose JK. Vesicular stomatitis virus G proteins with altered glycosylation sites display temperature-sensitive intracellular transport and are subject to aberrant intermolecular disulfide bonding. J Biol Chem. 1988 Apr 25;263(12):5955–5960. [PubMed]
  • Machamer CE, Doms RW, Bole DG, Helenius A, Rose JK. Heavy chain binding protein recognizes incompletely disulfide-bonded forms of vesicular stomatitis virus G protein. J Biol Chem. 1990 Apr 25;265(12):6879–6883. [PubMed]
  • Mazzarella RA, Green M. ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94). J Biol Chem. 1987 Jun 25;262(18):8875–8883. [PubMed]
  • Minami Y, Weissman AM, Samelson LE, Klausner RD. Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1987 May;84(9):2688–2692. [PubMed]
  • Moore MW, Carbone FR, Bevan MJ. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. [PubMed]
  • Morrison BD, Swanson ML, Sweet LJ, Pessin JE. Insulin-dependent covalent reassociation of isolated alpha beta heterodimeric insulin receptors into an alpha 2 beta 2 heterotetrameric disulfide-linked complex. J Biol Chem. 1988 Jun 5;263(16):7806–7813. [PubMed]
  • Ng DT, Randall RE, Lamb RA. Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface. J Cell Biol. 1989 Dec;109(6 Pt 2):3273–3289. [PMC free article] [PubMed]
  • Novikoff PM, Tulsiani DR, Touster O, Yam A, Novikoff AB. Immunocytochemical localization of alpha-D-mannosidase II in the Golgi apparatus of rat liver. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4364–4368. [PubMed]
  • Nuchtern JG, Bonifacino JS, Biddison WE, Klausner RD. Brefeldin A implicates egress from endoplasmic reticulum in class I restricted antigen presentation. Nature. 1989 May 18;339(6221):223–226. [PubMed]
  • Owen MJ, Kissonerghis AM, Lodish HF. Biosynthesis of HLA-A and HLA-B antigens in vivo. J Biol Chem. 1980 Oct 25;255(20):9678–9684. [PubMed]
  • Ozato K, Hansen TH, Sachs DH. Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex. J Immunol. 1980 Dec;125(6):2473–2477. [PubMed]
  • Palade G. Intracellular aspects of the process of protein synthesis. Science. 1975 Aug 1;189(4200):347–358. [PubMed]
  • Pfeffer SR, Rothman JE. Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi. Annu Rev Biochem. 1987;56:829–852. [PubMed]
  • Ploegh HL, Cannon LE, Strominger JL. 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. [PubMed]
  • Rose JK, Doms RW. Regulation of protein export from the endoplasmic reticulum. Annu Rev Cell Biol. 1988;4:257–288. [PubMed]
  • Salter RD, Cresswell P. Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid. EMBO J. 1986 May;5(5):943–949. [PubMed]
  • Saraste J, Kuismanen E. Pre- and post-Golgi vacuoles operate in the transport of Semliki Forest virus membrane glycoproteins to the cell surface. Cell. 1984 Sep;38(2):535–549. [PubMed]
  • Sege K, Rask L, Peterson PA. Role of beta2-microglobulin in the intracellular processing of HLA antigens. Biochemistry. 1981 Aug 4;20(16):4523–4530. [PubMed]
  • Smith MH, Parker JM, Hodges RS, Barber BH. The preparation and characterization of anti-peptide heteroantisera recognizing subregions of the intracytoplasmic domain of class I H-2 antigens. Mol Immunol. 1986 Oct;23(10):1077–1092. [PubMed]
  • Tartakoff AM. Temperature and energy dependence of secretory protein transport in the exocrine pancreas. EMBO J. 1986 Jul;5(7):1477–1482. [PubMed]
  • Townsend A, Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. [PubMed]
  • Townsend AR, Bastin J, Gould K, Brownlee GG. Cytotoxic T lymphocytes recognize influenza haemagglutinin that lacks a signal sequence. Nature. 1986 Dec 11;324(6097):575–577. [PubMed]
  • Townsend A, Ohlén C, Bastin J, Ljunggren HG, Foster L, Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. [PubMed]
  • Townsend A, Elliott T, Cerundolo V, Foster L, Barber B, Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. [PubMed]
  • Vogel RH, Provencher SW, von Bonsdorff CH, Adrian M, Dubochet J. Envelope structure of Semliki Forest virus reconstructed from cryo-electron micrographs. Nature. 1986 Apr 10;320(6062):533–535. [PubMed]
  • Wiedmann M, Huth A, Rapoport TA. Xenopus oocytes can secrete bacterial beta-lactamase. Nature. 1984 Jun 14;309(5969):637–639. [PubMed]
  • Williams DB, Swiedler SJ, Hart GW. Intracellular transport of membrane glycoproteins: two closely related histocompatibility antigens differ in their rates of transit to the cell surface. J Cell Biol. 1985 Sep;101(3):725–734. [PMC free article] [PubMed]
  • Williams DB, Borriello F, Zeff RA, Nathenson SG. Intracellular transport of class I histocompatibility molecules. Influence of protein folding on transport to the cell surface. J Biol Chem. 1988 Apr 5;263(10):4549–4560. [PubMed]
  • Williams DB, Barber BH, Flavell RA, Allen H. Role of beta 2-microglobulin in the intracellular transport and surface expression of murine class I histocompatibility molecules. J Immunol. 1989 Apr 15;142(8):2796–2806. [PubMed]
  • Yewdell JW, Bennink JR, Hosaka Y. Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. Science. 1988 Feb 5;239(4840):637–640. [PubMed]
  • Yewdell JW, Yellen A, Bächi T. Monoclonal antibodies localize events in the folding, assembly, and intracellular transport of the influenza virus hemagglutinin glycoprotein. Cell. 1988 Mar 25;52(6):843–852. [PubMed]
  • Yewdell JW, Bennink JR. Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science. 1989 Jun 2;244(4908):1072–1075. [PubMed]
  • Yokoyama K, Geier SS, Uehara H, Nathenson SG. Secondary structure of the murine histocompatibility alloantigen H-2Kb: relationship between heavy chain, beta 2-microglobulin, and antigenic reactivity. Biochemistry. 1985 Jun 4;24(12):3002–3006. [PubMed]
  • Yu S, Sher B, Kudryk B, Redman CM. Intracellular assembly of human fibrinogen. J Biol Chem. 1983 Nov 25;258(22):13407–13410. [PubMed]

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