Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape

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Pathogens such as HIV can enter cells by fusion at the plasma membrane for delivery in the cytosol, or by internalization in endolysosomal vesicles. Pathogens can be degraded in these various compartments into peptides (epitopes) displayed at the cell surface by MHC-I. The presentation of pathogen-derived peptides triggers the activation of T cell immune responses and the clearance of infected cells. How the diversity of compartments in which HIV traffics combined with the diversity of HIV sequences affects the degradation of HIV and the recognition of infected cells by immune cells is not understood. We compared the degradation of HIV proteins in subcellular compartments of dendritic cells and macrophages, two cell types targeted by HIV and the subsequent presentation of epitopes to T cells. We show variable degradation patterns of HIV according to compartments, and the preferential production and superior intracellular stability of immunodominant epitopes corresponding to stronger T cell responses. Frequent mutations in immunodominant epitopes during acute infection resulted in decreased production and intracellular stability of these epitopes. Together these results demonstrate the importance of protein degradation patterns in shaping immunodominant epitopes and the contribution of impaired epitope production in all cellular compartments to immune escape during HIV infection.

Vyšlo v časopise: Variable Processing and Cross-presentation of HIV by Dendritic Cells and Macrophages Shapes CTL Immunodominance and Immune Escape. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004725
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004725

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1. Yewdell JW Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses. Immunity. 2006;25: 533–543. 17046682

2. Altfeld M, Kalife ET, Qi Y, Streeck H, Lichterfeld M, Johnston MN, et al. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1. PLoS Med. 2006;3: e403. 17076553

3. Turnbull EL, Wong M, Wang S, Wei X, Jones NA, Conrod KE, et al. Kinetics of expansion of epitope-specific T cell responses during primary HIV-1 infection. J Immunol. 2009;182: 7131–7145. doi: 10.4049/jimmunol.0803658 19454710

4. Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med. 1997;3: 205–211. 9018240

5. Allen TM, Altfeld M, Geer SC, Kalife ET, Moore C, O'Sullivan K M, et al. Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. J Virol. 2005;79: 13239–13249. 16227247

6. Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, Addo M, et al. Adaptation of HIV-1 to human leukocyte antigen class I. Nature. 2009;458: 641–645. doi: 10.1038/nature07746 19242411

7. Liu MK, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, et al. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest. 2013;123: 380–393. doi: 10.1172/JCI65330 23221345

8. Oxenius A, Price DA, Trkola A, Edwards C, Gostick E, Zhang HT, et al. Loss of viral control in early HIV-1 infection is temporally associated with sequential escape from CD8+ T cell responses and decrease in HIV-1-specific CD4+ and CD8+ T cell frequencies. J Infect Dis. 2004;190: 713–721. 15272399

9. Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, et al. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog. 2009;5: e1000365. doi: 10.1371/journal.ppat.1000365 19343217

10. Chen W, Anton LC, Bennink JR, Yewdell JW Dissecting the multifactorial causes of immunodominance in class I-restricted T cell responses to viruses. Immunity. 2000;12: 83–93. 10661408

11. Bihl F, Frahm N, Di Giammarino L, Sidney J, John M, Yusim K, et al. Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses. J Immunol. 2006;176: 4094–4101. 16547245

12. Osuna CE, Gonzalez AM, Chang HH, Hung AS, Ehlinger E, Anasti K, et al. TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys. PLoS Pathog. 2014;10: e1004069. doi: 10.1371/journal.ppat.1004069 24743648

13. Schmidt J, Neumann-Haefelin C, Altay T, Gostick E, Price DA, Lohmann V, et al. Immunodominance of HLA-A2-restricted hepatitis C virus-specific CD8+ T cell responses is linked to naive-precursor frequency. J Virol. 2011;85: 5232–5236. doi: 10.1128/JVI.00093-11 21367907

14. Probst HC, Tschannen K, Gallimore A, Martinic M, Basler M, Dumrese T, et al. Immunodominance of an antiviral cytotoxic T cell response is shaped by the kinetics of viral protein expression. J Immunol. 2003;171: 5415–5422. 14607945

15. Schmidt J, Iversen AK, Tenzer S, Gostick E, Price DA, Lohmann V, et al. Rapid antigen processing and presentation of a protective and immunodominant HLA-B*27-restricted hepatitis C virus-specific CD8+ T-cell epitope. PLoS Pathog. 2012;8: e1003042. doi: 10.1371/journal.ppat.1003042 23209413

16. Tenzer S, Wee E, Burgevin A, Stewart-Jones G, Friis L, Lamberth K, et al. Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance. Nat Immunol. 2009;10: 636–646. doi: 10.1038/ni.1728 19412183

17. Le Gall S, Stamegna P, Walker BD Portable flanking sequences modulate CTL epitope processing. J Clin Invest. 2007;117: 3563–3575. 17975674

18. Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A, Tomura M, et al. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity. 2011;34: 85–95. doi: 10.1016/j.immuni.2010.12.011 21194983

19. Fonteneau JF, Kavanagh DG, Lirvall M, Sanders C, Cover TL, Bhardwaj N, et al. Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells. Blood. 2003;102: 4448–4455. 12933572

20. Larsson M, Fonteneau JF, Lirvall M, Haslett P, Lifson JD, Bhardwaj N Activation of HIV-1 specific CD4 and CD8 T cells by human dendritic cells: roles for cross-presentation and non-infectious HIV-1 virus. AIDS. 2002;16: 1319–1329. 12131208

21. Maranon C, Desoutter JF, Hoeffel G, Cohen W, Hanau D, Hosmalin A Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes. Proc Natl Acad Sci U S A. 2004;101: 6092–6097. 15079077

22. Buseyne F, Le Gall S, Boccaccio C, Abastado JP, Lifson JD, Arthur LO, et al. MHC-I-restricted presentation of HIV-1 virion antigens without viral replication. Nat Med. 2001;7: 344–349. 11231634

23. Sabado RL, Babcock E, Kavanagh DG, Tjomsland V, Walker BD, Lifson JD, et al. Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1. Eur J Immunol. 2007;37: 1752–1763. 17534864

24. Tjomsland V, Ellegard R, Burgener A, Mogk K, Che KF, Westmacott G, et al. Complement opsonization of HIV-1 results in a different intracellular processing pattern and enhanced MHC class I presentation by dendritic cells. Eur J Immunol. 2013;43: 1470–1483. doi: 10.1002/eji.201242935 23526630

25. Belizaire R, Unanue ER Targeting proteins to distinct subcellular compartments reveals unique requirements for MHC class I and II presentation. Proc Natl Acad Sci U S A. 2009;106: 17463–17468. doi: 10.1073/pnas.0908583106 19805168

26. Huang XL, Fan Z, Zheng L, Borowski L, Li H, Thomas EK, et al. Priming of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cell responses by dendritic cells loaded with HIV-1 proteins. J Infect Dis. 2003;187: 315–319. 12552458

27. Colbert JD, Matthews SP, Miller G, Watts C Diverse regulatory roles for lysosomal proteases in the immune response. Eur J Immunol. 2009;39: 2955–2965. doi: 10.1002/eji.200939650 19637232

28. Shen L, Sigal LJ, Boes M, Rock KL Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Immunity. 2004;21: 155–165. 15308097

29. Fonteneau JF, Gilliet M, Larsson M, Dasilva I, Munz C, Liu YJ, et al. Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity. Blood. 2003;101: 3520–3526. 12511409

30. Lucchiari-Hartz M, van Endert PM, Lauvau G, Maier R, Meyerhans A, Mann D, et al. Cytotoxic T lymphocyte epitopes of HIV-1 Nef: Generation of multiple definitive major histocompatibility complex class I ligands by proteasomes. J Exp Med. 2000;191: 239–252. 10637269

31. Geier E, Pfeifer G, Wilm M, Lucchiari-Hartz M, Baumeister W, Eichmann K, et al. A giant protease with potential to substitute for some functions of the proteasome. Science. 1999;283: 978–981. 9974389

32. Lutz MB, Rovere P, Kleijmeer MJ, Rescigno M, Assmann CU, Oorschot VM, et al. Intracellular routes and selective retention of antigens in mildly acidic cathepsin D/lysosome-associated membrane protein-1/MHC class II-positive vesicles in immature dendritic cells. J Immunol. 1997;159: 3707–3716. 9378956

33. Kamphorst AO, Guermonprez P, Dudziak D, Nussenzweig MC Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes. J Immunol. 2010;185: 3426–3435. doi: 10.4049/jimmunol.1001205 20729332

34. Lazaro E, Godfrey SB, Stamegna P, Ogbechie T, Kerrigan C, Zhang M, et al. Differential HIV epitope processing in monocytes and CD4 T cells affects cytotoxic T lymphocyte recognition. J Infect Dis. 2009;200: 236–243. doi: 10.1086/599837 19505257

35. Dinter J, Gourdain P, Lai NY, Duong E, Bracho-Sanchez E, Rucevic M, et al. Different Antigen-Processing Activities in Dendritic Cells, Macrophages, and Monocytes Lead to Uneven Production of HIV Epitopes and Affect CTL Recognition. J Immunol. 2014.

36. Steers NJ, Currier JR, Kijak GH, di Targiani RC, Saxena A, Marovich MA, et al. Cell type-specific proteasomal processing of HIV-1 Gag-p24 results in an altered epitope repertoire. J Virol. 2011;85: 1541–1553. doi: 10.1128/JVI.01790-10 21106750

37. Vaithilingam A, Lai NY, Duong E, Boucau J, Xu Y, Shimada M, et al. A simple methodology to assess endolysosomal protease activity involved in antigen processing in human primary cells. BMC Cell Biol. 2013;14: 35. doi: 10.1186/1471-2121-14-35 23937268

38. Steers NJ, Ratto-Kim S, de Souza MS, Currier JR, Kim JH, Michael NL, et al. HIV-1 envelope resistance to proteasomal cleavage: implications for vaccine induced immune responses. PLoS One. 2012;7: e42579. doi: 10.1371/journal.pone.0042579 22880042

39. Allen TM, Altfeld M, Yu XG, O'Sullivan KM, Lichterfeld M, Le Gall S, et al. Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection. J Virol. 2004;78: 7069–7078. 15194783

40. Draenert R, Le Gall S, Pfafferott KJ, Leslie AJ, Chetty P, Brander C, et al. Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection. J Exp Med. 2004;199: 905–915. 15067030

41. Yokomaku Y, Miura H, Tomiyama H, Kawana-Tachikawa A, Takiguchi M, Kojima A, et al. Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are major escape mechanisms from CTL immune pressure in human immunodeficiency virus type 1 infection. J Virol. 2004;78: 1324–1332. 14722287

42. Zhang SC, Martin E, Shimada M, Godfrey SB, Fricke J, Locastro S, et al. Aminopeptidase substrate preference affects HIV epitope presentation and predicts immune escape patterns in HIV-infected individuals. J Immunol. 2012;188: 5924–5934. doi: 10.4049/jimmunol.1200219 22586036

43. Streeck H, Frahm N, Walker BD The role of IFN-gamma Elispot assay in HIV vaccine research. Nat Protoc. 2009;4: 461–469. doi: 10.1038/nprot.2009.7 19282851

44. Lazaro E, Kadie C, Stamegna P, Zhang SC, Gourdain P, Lai NY, et al. Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape. J Clin Invest. 2011;121: 2480–2492. doi: 10.1172/JCI44932 21555856

45. Trombetta ES, Ebersold M, Garrett W, Pypaert M, Mellman I Activation of lysosomal function during dendritic cell maturation. Science. 2003;299: 1400–1403. 12610307

46. Yusim K, Korber BTM, Brander C, Barouch D, de Boer R, Haynes BF, et al. HIV Molecular Immunology 2013. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, New Mexico. 2013.

47. Goulder PJ, Bunce M, Krausa P, McIntyre K, Crowley S, Morgan B, et al. Novel, cross-restricted, conserved, and immunodominant cytotoxic T lymphocyte epitopes in slow progressors in HIV type 1 infection. AIDS Res Hum Retroviruses. 1996;12: 1691–1698. 8959245

48. Friedrich D, Jalbert E, Dinges WL, Sidney J, Sette A, Huang Y, et al. Vaccine-induced HIV-specific CD8+ T cells utilize preferential HLA alleles and target-specific regions of HIV-1. J Acquir Immune Defic Syndr. 2011;58: 248–252. doi: 10.1097/QAI.0b013e318228f992 21709567

49. Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science. 2005;307: 1630–1634. 15761154

50. Kourjian G, Xu Y, Mondesire-Crump I, Shimada M, Gourdain P, Le Gall S Sequence-specific alterations of epitope production by HIV protease inhibitors. J Immunol. 2014;192: 3496–3506. doi: 10.4049/jimmunol.1302805 24616479

51. Herberts CA, Neijssen JJ, de Haan J, Janssen L, Drijfhout JW, Reits EA, et al. Cutting edge: HLA-B27 acquires many N-terminal dibasic peptides: coupling cytosolic peptide stability to antigen presentation. J Immunol. 2006;176: 2697–2701. 16493024

52. Frahm N, Adams S, Kiepiela P, Linde CH, Hewitt HS, Lichterfeld M, et al. HLA-B63 presents HLA-B57/B58-restricted cytotoxic T-lymphocyte epitopes and is associated with low human immunodeficiency virus load. J Virol. 2005;79: 10218–10225. 16051815

53. Brockman MA, Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, et al. Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. J Virol. 2007;81: 12608–12618. 17728232

54. Miura T, Brockman MA, Schneidewind A, Lobritz M, Pereyra F, Rathod A, et al. HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphocyte [corrected] recognition. J Virol. 2009;83: 2743–2755. doi: 10.1128/JVI.02265-08 19116253

55. Pereyra F, Heckerman D, Carlson JM, Kadie C, Soghoian DZ, Karel D, et al. HIV control is mediated in part by CD8+ T-cell targeting of specific epitopes. J Virol. 2014.

56. Luckey CJ, King GM, Marto JA, Venketeswaran S, Maier BF, Crotzer VL, et al. Proteasomes can either generate or destroy MHC class I epitopes: evidence for nonproteasomal epitope generation in the cytosol. J Immunol. 1998;161: 112–121. 9647214

57. Lopez D, Del Val M Selective involvement of proteasomes and cysteine proteases in MHC class I antigen presentation. J Immunol. 1997;159: 5769–5772. 9550370

58. Burster T, Beck A, Tolosa E, Schnorrer P, Weissert R, Reich M, et al. Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells. J Immunol. 2005;175: 5940–5949. 16237087

59. Yang B, Hahn YS, Hahn CS, Braciale TJ The requirement for proteasome activity class I major histocompatibility complex antigen presentation is dictated by the length of preprocessed antigen. J Exp Med. 1996;183: 1545–1552. 8666912

60. Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol. 1999;1: 362–368. 10559964

61. Lev A, Takeda K, Zanker D, Maynard JC, Dimberu P, Waffarn E, et al. The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation. Immunity. 2008;28: 787–798. doi: 10.1016/j.immuni.2008.04.015 18549799

62. van Montfoort N, Camps MG, Khan S, Filippov DV, Weterings JJ, Griffith JM, et al. Antigen storage compartments in mature dendritic cells facilitate prolonged cytotoxic T lymphocyte cross-priming capacity. Proc Natl Acad Sci U S A. 2009;106: 6730–6735. doi: 10.1073/pnas.0900969106 19346487

63. Chateau MT, Robert-Hebmann V, Devaux C, Lazaro JB, Canard B, Coux O Human monocytes possess a serine protease activity capable of degrading HIV-1 reverse transcriptase in vitro. Biochem Biophys Res Commun. 2001;285: 863–872. 11467830

64. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, et al. Differential antigen processing by dendritic cell subsets in vivo. Science. 2007;315: 107–111. 17204652

65. Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, Huang Y, et al. Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci U S A. 2011;108: 2384–2389. doi: 10.1073/pnas.1019547108 21262813

66. Igyarto BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity. 2011;35: 260–272. doi: 10.1016/j.immuni.2011.06.005 21782478

67. Duclos S, Clavarino G, Rousserie G, Goyette G, Boulais J, Camossetto V, et al. The endosomal proteome of macrophage and dendritic cells. Proteomics. 2011;11: 854–864. doi: 10.1002/pmic.201000577 21280226

68. Savina A, Jancic C, Hugues S, Guermonprez P, Vargas P, Moura IC, et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell. 2006;126: 205–218. 16839887

69. Mantegazza AR, Savina A, Vermeulen M, Perez L, Geffner J, Hermine O, et al. NADPH oxidase controls phagosomal pH and antigen cross-presentation in human dendritic cells. Blood. 2008;112: 4712–4722. doi: 10.1182/blood-2008-01-134791 18682599

70. Rucevic M, Boucau J, Dinter J, Kourjian G, Le Gall S Mechanisms of HIV protein degradation into epitopes: implications for vaccine design. Viruses. 2014;6: 3271–3292. doi: 10.3390/v6083271 25196483

71. Goulder PJ, Watkins DI HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol. 2004;4: 630–640. 15286729

72. Ranasinghe SR, Kramer HB, Wright C, Kessler BM, di Gleria K, Zhang Y, et al. The antiviral efficacy of HIV-specific CD8(+) T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate. PLoS Pathog. 2011;7: e1001341. doi: 10.1371/journal.ppat.1001341 21589893

73. Tanuma J, Fujiwara M, Teruya K, Matsuoka S, Yamanaka H, Gatanaga H, et al. HLA-A*2402-restricted HIV-1-specific cytotoxic T lymphocytes and escape mutation after ART with structured treatment interruptions. Microbes Infect. 2008;10: 689–698. doi: 10.1016/j.micinf.2008.03.007 18462973

74. Ammaranond P, van Bockel DJ, Petoumenos K, McMurchie M, Finlayson R, Middleton MG, et al. HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome. J Immunol. 2011;186: 479–488. doi: 10.4049/jimmunol.0903227 21115730

75. Burton DR, Ahmed R, Barouch DH, Butera ST, Crotty S, Godzik A, et al. A Blueprint for HIV Vaccine Discovery. Cell Host Microbe. 2012;12: 396–407. doi: 10.1016/j.chom.2012.09.008 23084910

76. Stephenson KE, Barouch DH A global approach to HIV-1 vaccine development. Immunol Rev. 2013;254: 295–304. doi: 10.1111/imr.12073 23772627