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Corking the Bottleneck: The Transporter Associated with Antigen Processing as a Target for Immune Subversion by Viruses

  • Chapter
Viral Proteins Counteracting Host Defenses

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 269))

Abstract

In this chapter, mechanisms are reviewed that viruses use to inhibit the function of the peptide transporter associated with antigen processing (TAP), which translocates cytosolic peptides into the endoplasmic reticulum (ER) for binding to MHC class I molecules. Although some DNA viruses, such as adenovirus or EBV, downmodulate TAP expression on the transcriptional level, members of the alpha and beta subfamily of herpesviruses, such as herpes simplex virus (HSV) and human cytomegalovirus (HCMV), express proteins that bind to TAP and interfere with peptide translocation. The modes of action of the HSV-encoded cytosolic TAP inhibitor ICP47 and the HCMV-encoded ER-resident TAP inhibitor gpUS6 are discussed in detail. Viral interference with antigen presentation through TAP inhibition is not only relevant for the immunobiology of persistent viral infections but also contributes to the understanding of the translocation mechanism utilized by the ATP-binding cassette transporter TAP.

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References

  • Abele R, Tampé R (1999) Function of the transport complex TAP in cellular immune recognition. Biochim Biophys Acta 1461:405–419

    PubMed  CAS  Google Scholar 

  • Ahn K, Meyer TH, Uebel S, Sempe P, Djaballah H, Yang Y, Peterson PA, Früh K, Tampe R (1996a) Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47. EMBO J 15:3247–3255

    PubMed  CAS  Google Scholar 

  • Ahn K, Angulo A, Ghazal P, Peterson PA, Yang Y, Früh K (1996b) Human cytomegalovirus inhibits antigen presentation by a sequential multistep process. Proc Natl Acad Sei USA 93:10990–10995

    CAS  Google Scholar 

  • Ahn K, Gruhler A, Galocha B, Jones TR, Wiertz EJ, Ploegh HL, Peterson PA, Yang Y, Früh K (1997) The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity 6:613–621

    PubMed  CAS  Google Scholar 

  • Ambagala AP, Hinkley S, Srikumaran S (2000) An early Pseudorabies virus protein down-regulates porcine MHC class I expression by inhibition of transporter associated with antigen processing (TAP). J Immunol 164:93–99

    PubMed  CAS  Google Scholar 

  • Andersson M, Pääbo S, Nilsson T, Peterson PA (1985) Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance. Cell 43:215–222

    PubMed  CAS  Google Scholar 

  • Bangia N, Lehner PJ, Hughes EA, Surman M, Cresswell P (1999) The N-terminal region of tapasin is required to stabilize the MHC class I loading complex. Eur J Immunol 29:1858–1870

    PubMed  CAS  Google Scholar 

  • Barnden MJ, Purcell AW, Gorman J J, McCluskey J (2000) Tapasin-mediated retention and optimization of peptide ligands during the assembly of class I molecules. J Immunol 165:322–30

    PubMed  CAS  Google Scholar 

  • Beersma MF, Bijlmakers MJ, Ploegh HL (1993) Human cytomegalovirus down-regulates HLA class I expression by reducing the stability of class I H chains. J Immunol 151:4455–4464

    PubMed  CAS  Google Scholar 

  • Bennett EM, Bennink JR, Yewdell JW, Brodsky FM (1999) Cutting edge: adenovirus E19 has two mechanisms for affecting class I MHC expression. J Immunol 162:5049–5052

    PubMed  CAS  Google Scholar 

  • Benz C, Hengel H (2000) MHC class I-subversive gene functions of cytomegalovirus and their regulation by interferons — an intricate balance. Virus Genes 21:39–47

    PubMed  CAS  Google Scholar 

  • Borrego F, Ulbrecht M, Weiss EH, Coligan JE, Brooks AG (1998) Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. J Exp Med 187:813–818

    PubMed  CAS  Google Scholar 

  • Brander C, Suscovich T, Lee Y, Nguyen PT, O’Connor P, Seebach J, Jones NG, van Gorder M, Walker BD, Scadden DT (2000) Impaired CTL recognition of cells latently infected with Kaposi’s sarcoma-associated herpes virus. J Immunol 165:2077–2083

    PubMed  CAS  Google Scholar 

  • Braud VM, Allan DS, Wilson D, McMichael AJ (1998a) TAP and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol 8:1–10

    PubMed  CAS  Google Scholar 

  • Braud VM, Allan DS, O’Callaghan CA, Soderstrom K, D’Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (1998b) HLA-E binds to natural killer cell receptors CD94/ NKG2 A, B and C. Nature 391:795–799

    PubMed  CAS  Google Scholar 

  • Burgert HG, Kvist S (1985) An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell 41:987–997

    PubMed  CAS  Google Scholar 

  • Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, Horsnell T. Hutchison CA 3d, Kouzarides T, Martignetti JA, Preddi E, Satchwell SC, Tomlinson P, Weston KM, Barrel 1 BG (1990) Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD 169. Curr Top Microbiol Immunol 154:125–169

    PubMed  CAS  Google Scholar 

  • Cromme FV, Airey J, Heemels MT, Ploegh HL, Keating PJ, Stern PL, Meijer CJ, Walboomers JM (1994a) Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J Exp Med 179:335–340

    PubMed  CAS  Google Scholar 

  • Cromme FV, van Bommel PF, Walboomers JM, Gallee MP, Stern PL, Kenemans P, Heimerhorst TJ, Stukart MJ, Meijer CJ (1994b) Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours. Br J Cancer 69:1176–1181

    PubMed  CAS  Google Scholar 

  • Eager KB, Williams J, Breiding D, Pan S, Knowles B, Appella E, Ricciardi RP (1985) Expression of histocompatibility antigens H-2K, -D, and -L is reduced in adenovirus-12-transformed mouse cells and is restored by interferon gamma. Proc Natl Acad Sei USA 82:5525–5529

    CAS  Google Scholar 

  • Elliott T (1997) Transporter associated with antigen processing. Adv Immunol 65:47–109

    PubMed  CAS  Google Scholar 

  • Fleming SB, McCaughan CA, Andrews AE, Nash AD, Mercer AA (1997) A homolog of interleukin-10 isencoded by the poxvirus orf virus. J Virol 71:4857–4861

    PubMed  CAS  Google Scholar 

  • Früh K, Ahn K, Djaballah H, Sempe P, van Endert PM, Tampe R, Peterson PA, Yang Y (1995) A viralinhibitor of peptide transporters for antigen presentation. Nature 375:415—418

    PubMed  Google Scholar 

  • Früh K, Yang Y (1999) Antigen presentation by MHC class I and its regulation by interferon y. Curr Opin Immunol 11:76–81

    PubMed  Google Scholar 

  • Galocha B, Hill A, Barnett BC, Dolan A, Raimondi A, Cook RF, Brunner J, McGeoch DJ, Ploegh HL (1997) The active site of ICP47, a herpes simplex virus-encoded inhibitor of the major histocompatibility complex (MHC)-encoded peptide transporter associated with antigen processing (TAP), maps to the NH2-terminal 35 residues. J Exp Med 185:1565–1572

    PubMed  CAS  Google Scholar 

  • Garbi N, Tan P, Diehl AD, Chambers BJ, Ljunggren HG, Momburg F, Hämmerling GJ (2000) Impaired immune responses and altered peptide repertoire in tapsin-dehcient mice. Nature Immunol 1:234–238

    CAS  Google Scholar 

  • Hengel H, Eßlinger C, Pool J, Goulmy E, Koszinowski UH (1995). Cytokines restore MHC class I complex formation and control antigen presentation in human cytomegalovirus-infected cells. J Gen Virol 76:2987–2997

    PubMed  CAS  Google Scholar 

  • Hengel H, Flohr T, Hämmerling GJ, Koszinowski UH, Momburg F (1996) Human cytomegalovirus inhibits peptide translocation into the endoplasmic reticulum for MHC class I assembly. J Gen Virol 77:2287–2296

    PubMed  CAS  Google Scholar 

  • Hengel H, Koopmann JO, Flohr T, Muranyi W, Goulmy E, Hämmerling GJ, Koszinowski UH, Momburg F (1997a) A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter. Immunity 6:623–632

    PubMed  CAS  Google Scholar 

  • Hengel H, Koszinowski UH (1997b) Interference with antigen processing by viruses. Curr Opin Immunol 9:470–76

    PubMed  CAS  Google Scholar 

  • Hewitt EW, Gupta SS, Lehner PJ (2001) The human cytomegalovirus gene product US6 inhibits ATP binding by TAP. EMBO J 20:387–396

    PubMed  CAS  Google Scholar 

  • Hill AB, Barnett BC, McMichael A J, McGeoch DJ (1994) HL A class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2. J Immunol 152:2736–2741

    PubMed  CAS  Google Scholar 

  • Hill A, Jugovic P, York I, Russ G, Bennink J, Yewdell J, Ploegh H, Johnson D (1995) Herpes simplex virus turns oif the TAP to evade host immunity. Nature 375:411–415

    PubMed  CAS  Google Scholar 

  • Hinkley S, Hill AB, Srikumaran S (1998) Bovine herpesvirus-1 infection affects the peptide transport activity in bovine cells. Virus Res 53:91–96

    PubMed  CAS  Google Scholar 

  • Hsu DH, de Waal Malefyt R, Fiorentino DF, Dang MN, Vieira P, de Vries J, Spits H, Mosmann TR, Moore KW (1990) Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. Science 250:830–832

    PubMed  CAS  Google Scholar 

  • Huard B, Früh K (2000) A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells. Eur J Immunol 30:509–515

    PubMed  CAS  Google Scholar 

  • Jones TR, Muzithras VP (1992) A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family. J Virol 66:2541–2546

    PubMed  CAS  Google Scholar 

  • Jones TR, Wiertz EJ, Sun L, Fish KN, Nelson JA, Ploegh HL (1996) Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proc Natl Acad Sei USA 93:11327–11333

    CAS  Google Scholar 

  • Jugovic P, Hill AM, Tomazin R, Ploegh H, Johnson DC (1998) Inhibition of major histocompatibility complex class I antigen presentation in pig and primate cells by herpes simplex virus type 1 and 2 ICP47. J Virol 72:5076–5084

    PubMed  CAS  Google Scholar 

  • Jun Y, Kim E, Jin M, Sung HC, Han H, Geraghty DE, Ahn K (2000) Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules. J Immunol 164: 805–811

    PubMed  CAS  Google Scholar 

  • Keating PJ, Cromme FV, Duggan-Keen M, Snijders PJ, Walboomers JM, Hunter RD, Dyer PA, Stern PL (1995) Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. Br J Cancer 72:405–411

    PubMed  CAS  Google Scholar 

  • Khanna R, Burrows SR, Argaet V, Moss DJ (1994) Endoplasmic reticulum signal sequence facilitated transport of peptide epitopes restores immunogenicity of an antigen processing defective tumour cell line. Int Immunol 6:639–645

    PubMed  CAS  Google Scholar 

  • Khanna R, Busson P, Burrows SR, Raffoux C, Moss DJ, Nicholls JM, Cooper L (1998) Molecular characterization of antigen-processing function in nasopharyngeal carcinoma (NPC): evidence for efficient presentation of Epstein-Barr virus cytotoxic T-cell epitopes by NPC cells. Cancer Res 58:310–314

    PubMed  CAS  Google Scholar 

  • King NJ, Maxwell LE, Kesson AM (1989) Induction of class I major histocompatibility complex antigen expression by West Nile virus on y interferon-refractory early murine trophoblast cells. Proc Natl Acad Sei USA 86:911–915

    CAS  Google Scholar 

  • Knittler MR, Alberts P, Deverson EV, Howard JC (1999) Nucleotide binding by TAP mediates association with peptide and release of assembled MHC class I molecules. Curr Biol 9:999–1008

    PubMed  CAS  Google Scholar 

  • Koppers-Lalic D, Rijsewijk FAM, Verschuren SBE, van Gaans-van den Brink JAM, Neisig A, Ressing ME, Neefjes J, Wiertz EJHJ (2001) The UL41-encoded virion host shutoff (vhs) protein and vhs-independent mechanisms are responsible for down-regulation of MHC class I molecules by bovine herpesvirus 1. J Gen Virol 82:2071–2081

    PubMed  CAS  Google Scholar 

  • Kotenko SV, Saccani S, Izotova LS, Mirochnitchenko OV, Pestka S (2000) Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc Natl Acad Sei USA 97:1695–1700

    CAS  Google Scholar 

  • Kushner DB, Pereira DS, Liu X, Graham FL, Ricciardi RP (1996) The first exon of Adl2 El A excluding the transactivation domain mediates differential binding of COUP-TF and NF-kB to the MHC class I enhancer in transformed cells. Oncogene 12:143–151

    PubMed  CAS  Google Scholar 

  • Lacaille VG, Androlewicz MJ (1998) Herpes simplex virus inhibitor ICP47 destabilizes the transporter associated with antigen processing (TAP) heterodimer. J Biol Chem 273:17386–17390

    PubMed  CAS  Google Scholar 

  • Lee SP, Constandinou CM, Thomas WA, Croom-Carter D, Blake NW, Murray PG, Crocker J, Rickinson AB (1998a) Antigen presenting phenotype of Hodgkin Reed-Sternberg cells: analysis of the HLA class I processing pathway and the effects of interleukin-10 on epstein-barr virus-specific cytotoxic T-cell recognition. Blood 92:1020–1030

    PubMed  CAS  Google Scholar 

  • Lee N, Goodlett DR, Ishitani A, Marquardt H, Geraghty DE (1998b) HLA-E surface expression depends on binding of TAP-dependent peptides derived from certain HLA class I signal sequences. J Immunol 160:4951–4960

    PubMed  CAS  Google Scholar 

  • Lehner PJ, Karttunen JT, Wilkinson GW, Cresswell P (1997) The human cytomegalovirus US6 glycoprotein inhibits transporter associated with antigen processing-dependent peptide translocation. Proc Natl Acad Sei USA 94:6904–6909

    CAS  Google Scholar 

  • Li Y, Salter-Cid L, Vitiello A, Preckel T, Lee JD, Angulo A, Cai Z, Peterson PA, Yang Y (2000) Regulation of transporter associated with antigen processing by phosphorylation. J Biol Chem 275:24130–24135

    PubMed  CAS  Google Scholar 

  • Liu Y, King N, Kesson A, Blanden RV, Mullbacher A (1989) Flavivirus infection up-regulates the expression of class I and class II major histocompatibility antigens on and enhances T cell recognition of astrocytes in vitro. J Neuroimmunol 21:157–168

    PubMed  CAS  Google Scholar 

  • Liu Y, Kitsis RN (1996) Induction of DNA synthesis and apoptosis in cardiac myocytes by El A oncoprotein. J Cell Biol 133:325–334

    PubMed  CAS  Google Scholar 

  • Ljunggren HG, Stam NJ, Ohlen C, Neefjes JJ, Hoglund P, Heemels MT, Bastin J, Schumacher TN, Townsend A, Kärre K, Ploegh HL (1990) Empty MHC class I molecules come out in the cold. Nature 346:476–480

    PubMed  CAS  Google Scholar 

  • Lockridge KM, Zhou SS, Kravitz RH, Johnson JL, Sawai ET, Blewett EL, Barry PA. (2000) Primate cytomegaloviruses encode and express an IL-10-like protein. Virology 268:272–280

    PubMed  CAS  Google Scholar 

  • Momburg F, Hämmerling GJ (1998) Generation and TAP-mediated transport of peptides for major histocompatibility complex class I molecules. Adv Immunol 68:191–256

    PubMed  CAS  Google Scholar 

  • Momburg F, Müllbacher A, Lobigs M (2001) Modulation of transporter associated with antigen processing (TAP)-mediated peptide import into the endoplasmic reticulum by flavivirus infection. J Virol 75:5663–5671

    PubMed  CAS  Google Scholar 

  • Momburg F, Roelse J, Hämmerling GJ, Neefjes J J (1994) Peptide size selection by the major histocompatibility complex-encoded peptide transporter. J Exp Med 179:1613–1623

    PubMed  CAS  Google Scholar 

  • Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR (1990) Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248: 1230–1234

    PubMed  CAS  Google Scholar 

  • Moore KW, O’Garra A, de Waal Malefyt R, Vieira P. Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190

    PubMed  CAS  Google Scholar 

  • Moss DJ, Khanna R, Sherritt M, Elliott SL, Burrows SR (1999) Developing immunotherapeutic strategies for the control of Epstein-Barr virus-associated malignancies. J Acquir Immune Defic Syndr 21: S80–S83

    PubMed  CAS  Google Scholar 

  • Müllbacher A, Lobigs M (1995) Up-regulation of MHC class I by flavivirus-induced peptide translocation into the endoplasmic reticulum. Immunity 3:207–214

    PubMed  Google Scholar 

  • Murray PG, Constandinou CM, Crocker J, Young LS, Ambinder RF (1998) Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin’s disease. Blood 92:2477–2483

    PubMed  CAS  Google Scholar 

  • Neumann L, Kraas W, Uebel S, Jung G, Tampé R (1997) The active domain of the herpes simplex virus protein ICP47: a potent inhibitor of the transporter associated with antigen processing. J Mol Biol 272:484–492

    PubMed  CAS  Google Scholar 

  • Neumann L, Tampe R (1999) Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding. J Mol Biol 294:1203–1213

    PubMed  CAS  Google Scholar 

  • Pamer E, Cresswell P (1998) Mechanisms of MHC class I-restricted antigen processing. Annu Rev Immunol 16:323–358

    PubMed  CAS  Google Scholar 

  • Paz P, Brouwenstijn N, Perry R, Shastri N (1999) Discrete proteolytic intermediates in the MHC class I antigen processing pathway and MHC I-dependent peptide trimming in the ER. Immunity 11:241–251

    PubMed  CAS  Google Scholar 

  • Ploegh HL (1998) Viral strategies of immune evasion. Science 280:248–253

    PubMed  CAS  Google Scholar 

  • Reits EA, Vos JC, Gromme M, Neefjes J (2000) The major substrates for TAP in vivo are derived from newly synthesized proteins. Nature 404:774–778

    PubMed  CAS  Google Scholar 

  • Rickinson AB, Kieff E (1996) Epstein-Barr Virus. In: Fields BN, Knipe DM, Howley PM (eds) Fields Virology. Lippincott-Raven, Philadelphia, pp 2397–2445

    Google Scholar 

  • Robb JA, Benirschke K, Barmeyer R (1986) Intrauterine latent herpes simplex virus infection: I. Spontaneous abortion. Hum Pathol 17:1196–1209

    PubMed  CAS  Google Scholar 

  • Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779

    PubMed  CAS  Google Scholar 

  • Rode HJ, Janssen W, Rosen-Wolff A, Bugert JJ, Thein P, Becker Y, Darai G (1993) The genome of equine herpesvirus type 2 harbors an interleukin 10 (ILlO)-likc gene. Virus Genes 7:111–116

    PubMed  CAS  Google Scholar 

  • Rotem-Yehudar R, Winograd S, Sela S, Coligan JE, Ehrlich R (1994) Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12. J Exp Med 180:477–488

    PubMed  CAS  Google Scholar 

  • Rotem-Yehudar R, Groettrup M, Soza A, Kloetzel PM, Ehrlich R (1996) LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12. J Exp Med 183:499–514

    PubMed  CAS  Google Scholar 

  • Rowe M, Khanna R, Jacob CA, Argaet V, Kelly A, Powis S, Beiich M, Croom-Carter D, Lee S, Burrows SR, Trowsdale J, Moss, DJ, Rickinson, AB (1995) Restoration of endogenous antigen processing in Burkitt’s lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression. Eur J Immunol 25:1374–1384

    PubMed  CAS  Google Scholar 

  • Salter RD, Cresswell P (1986) Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid. EMBO J 5:943–949

    PubMed  CAS  Google Scholar 

  • Schrier PI, Bernards R, Vaessen RT, Houweling A, van der Eb AJ (1983) Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. Nature 305:771–775

    PubMed  CAS  Google Scholar 

  • Schust DJ, Hill AB, Ploegh HL (1996) Herpes simplex virus blocks intracellular transport of HLA-G in placentally derived human cells. J Immunol 157:3375–3380

    PubMed  CAS  Google Scholar 

  • Seliger B, Maeurer MJ, Ferrone S (1997) TAP off — tumors on. Immunol Today 18:292–299

    PubMed  CAS  Google Scholar 

  • Seliger B, Maeurer MJ, Ferrone S (2000) Antigen-processing machinery breakdown and tumor growth. Immunol Today 21:455–464

    PubMed  CAS  Google Scholar 

  • Tomasec P, Braud VM, Rickards C, Powell MB, McSharry BP, Gadola S, Cerundolo V, Borysiewicz LK, McMichael A J, Wilkinson GW (2000). Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40. Science 287:1031–1033

    PubMed  CAS  Google Scholar 

  • Tomazin R, Hill AB, Jugovic P, York I, van Endert P, Ploegh HL, Andrews DW, Johnson DC (1996) Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP. EMBO J 15:3256–3266

    PubMed  CAS  Google Scholar 

  • Tomazin R, van Schoot NE, Goldsmith K, Jugovic P, Sempe P, Früh K, Johnson DC (1998) Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP. J Virol 72:2560–2563

    PubMed  CAS  Google Scholar 

  • Ulbrecht M, Martinozzi S, Grzeschik M, Hengel H, Eilwart JW, Pia M, Weiss EH (2000) Cutting edge: the human cytomegalovirus UL40 gene product contains a ligand for HLA-E and prevents NK cell-mediated lysis. J Immunol 164:5019–5022

    PubMed  CAS  Google Scholar 

  • van Endert PM (1999a) Genes regulating MHC class I processing of antigen. Curr Opin Immunol 11:82–88

    PubMed  Google Scholar 

  • van Endert PM (1999b) Role of nucleotides and peptide substrate for stability and functional state of the human ABC family transporters associated with antigen processing. J Biol Chem 274:14632–14638

    PubMed  Google Scholar 

  • Vambutas A, Bonagura VR, Steinberg BM (2000) Altered expression of TAP-1 and major histocompatibility complex class I in laryngeal papillomatosis: correlation of TAP-1 with disease. Clin Diagn Lab Immunol 7:79–85

    PubMed  CAS  Google Scholar 

  • Vos JC, Spee P, Momburg F, Neefjes J (1999a) Membrane topology and dimerization of the two subunits of the transporter associated with antigen processing reveal a three-domain structure. J Immunol 163:6679–6685

    PubMed  CAS  Google Scholar 

  • Vos JC, Reits EA, Wojcik-Jacobs E, Neefjes J (1999b) Head-head/tail-tail relative orientation of the pore-forming domains of the heterodimeric ABC transporter TAP. Curr Biol 10:1–7

    Google Scholar 

  • Watts C (1997) Capture and processing of exogenous antigens for presentation on MHC molecules. Annu Rev Immunol 15:821–50

    PubMed  CAS  Google Scholar 

  • Wiertz EJ, Jones TR, Sun L, Bogyo M, Geuze HJ, Ploegh HL (1996a) The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84:769–779

    PubMed  CAS  Google Scholar 

  • Wiertz EJ, Tortorella D, Bogyo M, Yu J, Mothes W, Jones TR, Rapoport TA, Ploegh HL (1996b) Sec61- mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384:432

    PubMed  CAS  Google Scholar 

  • Wright KL, White LC, Kelly A, Beck S, Trowsdale J, Ting JP (1995) Coordinate regulation of the human TAP1 and LMP2 genes from a shared bidirectional promoter. J Exp Med 181:1459–1471

    PubMed  CAS  Google Scholar 

  • Yamashita Y, Shimokata K, Mizuno S, Yamaguchi H, Nishiyama Y (1993) Down-regulation of the surface expression of class I MHC antigens by human cytomegalovirus. Virology 193:727–736

    PubMed  CAS  Google Scholar 

  • Yewdell JW, Norbury CC, Bennink JR (1999) Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: implications for generating CD8 + T cell responses to infectious agents, tumors, transplants, and vaccines. Adv Immunol 73:1–77

    PubMed  CAS  Google Scholar 

  • York IA, Roop C, Andrews DW, Riddell SR, Graham FL, Johnson DC (1994) A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77:525–535

    PubMed  CAS  Google Scholar 

  • Zeidler R, Eissner G, Meissner P, Uebel S, Tampe R, Lazis S, Hammerschmidt W (1997) Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 90:2390–2397

    PubMed  CAS  Google Scholar 

  • zur Hausen H (2000) Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 92:690–698

    Google Scholar 

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Authors and Affiliations

  1. Deutsches Krebsforschungszentrum, Department of Molecular Immunology, 69120, Heidelberg, Germany

    F. Momburg

  2. Robert Koch-Institut, Division of Viral Infections, 13353, Berlin, Germany

    H. Hengel

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  1. F. Momburg
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  2. H. Hengel
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Editors and Affiliations

  1. Max von Pettenkofer Institute, University of Munich, Pettenkoferstr. 9a, 80336, Munich, Germany

    Ulrich H. Koszinowski

  2. Robert Koch-Institut, Fachgebiet 1.2 Virale Infektionen, Nordufer 20, 13353, Berlin, Germany

    Hartmut Hengel

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Momburg, F., Hengel, H. (2002). Corking the Bottleneck: The Transporter Associated with Antigen Processing as a Target for Immune Subversion by Viruses. In: Koszinowski, U.H., Hengel, H. (eds) Viral Proteins Counteracting Host Defenses. Current Topics in Microbiology and Immunology, vol 269. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59421-2_4

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  • DOI: https://doi.org/10.1007/978-3-642-59421-2_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63974-6

  • Online ISBN: 978-3-642-59421-2

  • eBook Packages: Springer Book Archive

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