Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors

PLoS Pathogens

Volumn 12, Issue 12, 2016, Pages

  Dekhtiarenko, Iryna ^a   Ratts, Robert B ^b   Blatnik, Renata ^c,d   Lee, Lian N ^e   Fischer, Sonja ^a   Borkner, Lisa ^a   Oduro, Jennifer D ^a   Marandu, Thomas F ^a,f   Hoppe, Stephanie ^c,d   Ruzsics, Zsolt ^g   Sonnemann, Julia K ^a   Mansouri, Mandana ^h   Meyer, Christine ^b   Lemmermann, Niels A W ⁱ   Holtappels, Rafaela ⁱ   Arens, Ramon ^j   Klenerman, Paul ^e   Früh, Klaus ^b,h   Reddehase, Matthias J ⁱ   Riemer, Angelika B ^c,d   Cicin Sain, Luka ^a,k   more..

^a HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

^b TomegaVax Inc   (United States)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d German Centre for Infection Research (DZIF)   (Germany)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f UNIVERSITY OF DAR ES SALAAM   (Tanzania)

^g UNIVERSITY OF FREIBURG   (Germany)

^h OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

ⁱ UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^j LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^k HANNOVER MEDICAL SCHOOL   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CYTOMEGALOVIRUS VACCINE; EPITOPE; GAMMA INTERFERON; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PROTEASOME; PEPTIDE; RECOMBINANT VACCINE; VIRAL PROTEIN; VIRUS ANTIGEN; VIRUS VACCINE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN PRESENTATION; ARTICLE; BONE MARROW CELL; CARBOXY TERMINAL SEQUENCE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; COCULTURE; CONTROLLED STUDY; DRUG EFFICACY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; IMMUNOLOGICAL MEMORY; IN VITRO STUDY; IN VIVO STUDY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOUSE; MURINE CYTOMEGALOVIRUS; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN PROCESSING; SPLEEN CELL; VACCINATION; VIRUS RECOMBINANT; ANIMAL; HERPES VIRUS INFECTION; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; MUROMEGALOVIRUS; SITE DIRECTED MUTAGENESIS;

ANIMALS; ANTIGENS, VIRAL; CD8-POSITIVE T-LYMPHOCYTES; CHROMATOGRAPHY, LIQUID; EPITOPES, T-LYMPHOCYTE; FLOW CYTOMETRY; HERPESVIRIDAE INFECTIONS; IMMUNODOMINANT EPITOPES; IMMUNOLOGIC MEMORY; LYMPHOCYTE ACTIVATION; MASS SPECTROMETRY; MICE; MUROMEGALOVIRUS; MUTAGENESIS, SITE-DIRECTED; PEPTIDES; VACCINES, SYNTHETIC; VIRAL PROTEINS; VIRAL VACCINES;

EID: 85007591499     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1006072     Document Type: Article

References (60)

1. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85. doi: 10.1084/jem.2005088216147978
2. O'Hara GA, Welten SP, Klenerman P, Arens R, Memory T cell inflation: understanding cause and effect. Trends in immunology. 2012;33(2):84–90. doi: 10.1016/j.it.2011.11.00522222196
3. Klenerman P, Oxenius A, T cell responses to cytomegalovirus. Nature reviews Immunology. 2016.
4. Komatsu H, Sierro S, A VC, Klenerman P, Population analysis of antiviral T cell responses using MHC class I-peptide tetramers. Clinical and experimental immunology. 2003;134(1):9–12. doi: 10.1046/j.1365-2249.2003.02266.x12974748
5. Cicin-Sain L, Sylwester AW, Hagen SI, Siess DC, Currier N, Legasse AW, et al. Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. Journal of immunology. 2011;187(4):1722–32.
6. Karrer U, Wagner M, Sierro S, Oxenius A, Hengel H, Dumrese T, et al. Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses. J Virol. 2004;78(5):2255–64. doi: 10.1128/JVI.78.5.2255-2264.200414963122
7. Klyushnenkova EN, Kouiavskaia DV, Parkins CJ, Caposio P, Botto S, Alexander RB, et al. A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer. Journal of immunotherapy (Hagerstown, Md: 1997). 2012;35(5):390–9.
8. Dekhtiarenko I, Jarvis MA, Ruzsics Z, Čičin-Šain L, The Context of Gene Expression Defines the Immunodominance Hierarchy of Cytomegalovirus Antigens. The Journal of Immunology. 2013;190(7):3399–409. doi: 10.4049/jimmunol.120317323460738
9. Tsuda Y, Caposio P, Parkins CJ, Botto S, Messaoudi I, Cicin-Sain L, et al. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus. PLoS neglected tropical diseases. 2011;5(8):e1275. doi: 10.1371/journal.pntd.000127521858240
10. Schluns KS, Kieper WC, Jameson SC, Lefrancois L, Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nature immunology. 2000;1(5):426–32. doi: 10.1038/8086811062503
11. Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nature medicine. 2009;15(3):293–9. doi: 10.1038/nm.193519219024
12. Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011;473(7348):523–7. doi: 10.1038/nature1000321562493
13. Hansen SG, Piatak M, Jr.Ventura AB, Hughes CM, Gilbride RM, Ford JC, et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013;502(7469):100–4. doi: 10.1038/nature1251924025770
14. Picker LJ, Hansen SG, Lifson JD, New paradigms for HIV/AIDS vaccine development. Annu Rev Med. 2012;63:95–111. doi: 10.1146/annurev-med-042010-08564321942424
15. Podlech J, Holtappels R, Pahl-Seibert MF, Steffens HP, Reddehase MJ, Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection. J Virol. 2000;74(16):7496–507. 10906203
16. Holtappels R, Pahl-Seibert MF, Thomas D, Reddehase MJ, Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62L(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs. J Virol. 2000;74(24):11495–503. 11090146
17. Karrer U, Sierro S, Wagner M, Oxenius A, Hengel H, Koszinowski UH, et al. Memory inflation: continuous accumulation of antiviral CD8+ T cells over time. Journal of immunology. 2003;170(4):2022–9.
18. Munks MW, Cho KS, Pinto AK, Sierro S, Klenerman P, Hill AB, Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. Journal of immunology. 2006;177(1):450–8.
19. Sierro S, Rothkopf R, Klenerman P, Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection. European journal of immunology. 2005;35(4):1113–23. doi: 10.1002/eji.20042553415756645
20. Seckert CK, Griessl M, Buttner JK, Scheller S, Simon CO, Kropp KA, et al. Viral latency drives 'memory inflation': a unifying hypothesis linking two hallmarks of cytomegalovirus infection. Medical microbiology and immunology. 2012;201(4):551–66. doi: 10.1007/s00430-012-0273-y22991040
21. Maninger S, Bosse JB, Lemnitzer F, Pogoda M, Mohr CA, von Einem J, et al. M94 is essential for the secondary envelopment of murine cytomegalovirus. J Virol. 2011;85(18):9254–67. doi: 10.1128/JVI.00443-1121715482
22. Lin KY, Guarnieri FG, Staveley-O'Carroll KF, Levitsky HI, August JT, Pardoll DM, et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer research. 1996;56(1):21–6. 8548765
23. Gold MC, Munks MW, Wagner M, Koszinowski UH, Hill AB, Fling SP, The murine cytomegalovirus immunomodulatory gene m152 prevents recognition of infected cells by M45-specific CTL but does not alter the immunodominance of the M45-specific CD8 T cell response in vivo. Journal of immunology. 2002;169(1):359–65.
24. Holtappels R, Podlech J, Pahl-Seibert M-F, Jülch M, Thomas D, Simon CO, et al. Cytomegalovirus Misleads Its Host by Priming of CD8 T Cells Specific for an Epitope Not Presented in Infected Tissues. The Journal of Experimental Medicine. 2004;199(1):131–6. doi: 10.1084/jem.2003158214699084
25. Lemmermann NAW, Kropp KA, Seckert CK, Grzimek NKA, Reddehase MJ, Reverse Genetics Modification of Cytomegalovirus Antigenicity and Immunogenicity by CD8 T-Cell Epitope Deletion and Insertion. Journal of Biomedicine and Biotechnology. 2011;2011:812742. doi: 10.1155/2011/81274221253509
26. Holtappels R, Thomas D, Reddehase MJ, The efficacy of antigen processing is critical for protection against cytomegalovirus disease in the presence of viral immune evasion proteins. J Virol. 2009;83(18):9611–5. doi: 10.1128/JVI.00936-0919553308
27. Holzki JK, Dag F, Dekhtiarenko I, Rand U, Casalegno-Garduno R, Trittel S, et al. Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression. J Virol. 2015;89(19):9886–95. doi: 10.1128/JVI.01459-1526202227
28. Fink A, Lemmermann NA, Gillert-Marien D, Thomas D, Freitag K, Bohm V, et al. Antigen presentation under the influence of 'immune evasion' proteins and its modulation by interferon-gamma: implications for immunotherapy of cytomegalovirus infection with antiviral CD8 T cells. Medical microbiology and immunology. 2012;201(4):513–25. doi: 10.1007/s00430-012-0256-z22961126
29. Del Val M, Schlicht H-J, Ruppert T, Reddehase MJ, Koszinowski UH, Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991;66(6):1145–53. 1913805
30. Mueller SN, Heath W, McLain JD, Carbone FR, Jones CM, Characterization of two TCR transgenic mouse lines specific for herpes simplex virus. Immunol Cell Biol. 2002;80(2):156–63. doi: 10.1046/j.1440-1711.2002.01071.x11940116
31. Simon CO, Holtappels R, Tervo HM, Bohm V, Daubner T, Oehrlein-Karpi SA, et al. CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. J Virol. 2006;80(21):10436–56. doi: 10.1128/JVI.01248-0616928768
32. Farrington LA, Smith TA, Grey F, Hill AB, Snyder CM, Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection. Journal of immunology. 2013;190(7):3410–6.
33. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA, Zhan Y, et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006;25(1):153–62. doi: 10.1016/j.immuni.2006.04.01716860764
34. Torti N, Walton SM, Murphy KM, Oxenius A, Batf3 transcription factor-dependent DC subsets in murine CMV infection: differential impact on T-cell priming and memory inflation. European journal of immunology. 2011;41(9):2612–8. doi: 10.1002/eji.20104107521604258
35. Busche A, Jirmo AC, Welten SPM, Zischke J, Noack J, Constabel H, et al. Priming of CD8+ T Cells against Cytomegalovirus-Encoded Antigens Is Dominated by Cross-Presentation. The Journal of Immunology. 2013;190(6):2767–77. doi: 10.4049/jimmunol.120096623390296
36. Seckert CK, Renzaho A, Tervo HM, Krause C, Deegen P, Kuhnapfel B, et al. Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol. 2009;83(17):8869–84. doi: 10.1128/JVI.00870-0919535440
37. Dag F, Dolken L, Holzki J, Drabig A, Weingartner A, Schwerk J, et al. Reversible silencing of cytomegalovirus genomes by type I interferon governs virus latency. PLoS pathogens. 2014;10(2):e1003962. doi: 10.1371/journal.ppat.100396224586165
38. Seckert CK, Schader SI, Ebert S, Thomas D, Freitag K, Renzaho A, et al. Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency. Journal of General Virology. 2011;92(9):1994–2005.
39. Torti N, Walton SM, Brocker T, Rulicke T, Oxenius A, Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. PLoS pathogens. 2011;7(10):e1002313. doi: 10.1371/journal.ppat.100231322046127
40. Hutchinson S, Sims S, O'Hara G, Silk J, Gileadi U, Cerundolo V, et al. A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PloS one. 2011;6(2):e14646. doi: 10.1371/journal.pone.001464621304910
41. Colston JM, Bolinger B, Cottingham MG, Gilbert S, Klenerman P, Modification of Antigen Impacts on Memory Quality after Adenovirus Vaccination. Journal of immunology. 2016;196(8):3354–63.
42. Tenzer S, Peters B, Bulik S, Schoor O, Lemmel C, Schatz MM, et al. Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding. Cellular and molecular life sciences: CMLS. 2005;62(9):1025–37. doi: 10.1007/s00018-005-4528-215868101
43. Holtappels R, Lemmermann NA, Podlech J, Ebert S, Reddehase MJ, Reconstitution of CD8 T Cells Protective against Cytomegalovirus in a Mouse Model of Hematopoietic Cell Transplantation: Dynamics and Inessentiality of Epitope Immunodominance. Front Immunol. 2016;7:232. doi: 10.3389/fimmu.2016.0023227379095
44. Sijts EJ, Kloetzel PM, The role of the proteasome in the generation of MHC class I ligands and immune responses. Cellular and molecular life sciences: CMLS. 2011;68(9):1491–502. doi: 10.1007/s00018-011-0657-y21387144
45. Komlosh A, Momburg F, Weinschenk T, Emmerich N, Schild H, Nadav E, et al. A role for a novel luminal endoplasmic reticulum aminopeptidase in final trimming of 26 S proteasome-generated major histocompatability complex class I antigenic peptides. The Journal of biological chemistry. 2001;276(32):30050–6. doi: 10.1074/jbc.M10317720011373290
46. Nauerth M, Weiβbrich B, Knall R, Franz T, Dössinger G, Bet J, et al. TCR-ligand k(off)-rate predicts protective capacity of antigen-specific CD8(+) T cells for adoptive transfer. Science translational medicine. 2013;5(192):192ra87–ra87. doi: 10.1126/scitranslmed.300595823825303
47. Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science (New York, NY). 2013;340(6135):1237874.
48. Fehling H, Swat W, Laplace C, Kuhn R, Rajewsky K, Muller U, et al. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science (New York, NY). 1994;265(5176):1234–7.
49. Lemmermann NAW, Podlech J, Seckert CK, Kropp KA, Grzimek NKA, Reddehase MJ, Kabelitz D, Kaufmann HES, et al. 16—CD8 T-Cell Immunotherapy of Cytomegalovirus Disease in the Murine Model. In: Methods in Microbiology. Volume 37: Academic Press; 2010. p. 369–420.
50. Wallace ME, K R, Heath W. R., Carbone F. R., The cytotoxic T-Cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant. Journal of Virology. 1999;73:7619–26. 10438852
51. Tischer BK, Smith G, Osterrieder N, Braman J, En Passant Mutagenesis: A Two Step Markerless Red Recombination System. In: In Vitro Mutagenesis Protocols. Methods in Molecular Biology. 634: Humana Press; 2010. p. 421–30.
52. Dekhtiarenko I, Cicin-Sain L, Messerle M, Use of recombinant approaches to construct human cytomegalovirus mutants. Methods Mol Biol. 2014;1119:59–79. doi: 10.1007/978-1-62703-788-4_524639218
53. Bubeck A, Wagner M, Ruzsics Z, Lotzerich M, Iglesias M, Singh IR, et al. Comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication. J Virol. 2004;78(15):8026–35. doi: 10.1128/JVI.78.15.8026-8035.200415254174
54. Wagner M, Jonjic S, Koszinowski UH, Messerle M, Systematic excision of vector sequences from the BAC-cloned herpesvirus genome during virus reconstitution. J Virol. 1999;73(8):7056–60. 10400809
55. Jordan S, K J, Prager A., Mitrovic M., Jonjic S., Koszinowski U. H., Adler B., Virus Progeny of Murine Cytomegalovirus Bacterial Artificial Chromosome pSM3fr Show Reduced Growth in Salivary Glands due to a Fixed Mutation of MCK-2. Journal of Virology. 2011;85:10346–53. doi: 10.1128/JVI.00545-1121813614
56. Cicin-Sain L, Podlech J., Messerle M., Reddehase M. J., Koszinowski U. H., Frequent coinfection of cells explains functional in vivo complementation between cytomegalovirus variants in the multiply infected host. Journal of Virology. 2005;79:9492–502. doi: 10.1128/JVI.79.15.9492-9502.200516014912
57. Lang A, Brien JD, Nikolich-Žugich J, Inflation and Long-Term Maintenance of CD8 T Cells Responding to a Latent Herpesvirus Depend upon Establishment of Latency and Presence of Viral Antigens. The Journal of Immunology. 2009;183(12):8077–87. doi: 10.4049/jimmunol.080111720007576
58. Blaney JE, Nobusawa E, Brehm MA, Bonneau RH, Mylin LM, Fu T-M, et al. Immunization with a Single Major Histocompatibility Complex Class I-Restricted Cytotoxic T-Lymphocyte Recognition Epitope of Herpes Simplex Virus Type 2 Confers Protective Immunity. Journal of virology. 1998;72(12):9567–74. 9811690
59. Dudek NL, Tan CT, Gorasia DG, Croft NP, Illing PT, Purcell AW, Constitutive and inflammatory immunopeptidome of pancreatic beta-cells. Diabetes. 2012;61(11):3018–25. doi: 10.2337/db11-133322872234
60. Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014;515(7528):572–6. doi: 10.1038/nature1400125428506