Advertisement

Immunogenetics

, Volume 71, Issue 5–6, pp 407–420 | Cite as

Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms

  • Shawna L. Semple
  • George Heath
  • Darah Christie
  • Marsela Braunstein
  • Stephen C. Kales
  • Brian DixonEmail author
Original Article
  • 42 Downloads

Abstract

Major histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1β transcripts and homotypic aggregation of RTS11. S25-7 transcript levels remained unchanged in the gill, spleen, and liver and were found to be significantly decreased in head kidney beginning 24 h post-stimulation. Meanwhile, INVX transcript levels remained unchanged in all tissues studied. Both S25-7 and INVX proteins were produced in gill and spleen tissues but their expression was unaffected by immune system stimulation. Surprisingly, neither INVX nor S25-7 protein was detected in the secondary immune organ, the head kidney. Analysis of RTS11 cultures demonstrated that both INVX and S25-7 transcript levels significantly increased at 96 h and 120 h following PMA stimulation before returning to control levels at 168 h. Meanwhile, at the protein level in RTS11, S25-7 remained unchanged while INVX had a significant decrease at 168 h post-stimulation. These results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals.

Keywords

Invariant chain Phorbol myristate acetate Antigen presentation Rainbow trout RTS11 Adaptive immunity 

Notes

Acknowledgments

The authors would like to thank Martin Ryan for his technical assistance.

Funding information

The work presented in this paper was supported by the Natural Science and Engineering Research Council of Canada grant number 217529 and a Canada Research Chair to BD.

Compliance with ethical standards

All fish were kept and handled under a permit from the University of Waterloo Animal Care Committee according to CCAC guidelines. All procedures were performed following guidelines of the Animal Care Committee of the University of Waterloo.

Supplementary material

251_2019_1115_MOESM1_ESM.pdf (459 kb)
ESM 1 (PDF 458 kb)

References

  1. Albanesi C, Cavani A, Girolomoni G (1998) Interferon-gamma-stimulated human keratinocytes express genes necessary for the production of peptide-loaded MHC class II molecules. J Investig Dermatol 110:138–142CrossRefGoogle Scholar
  2. Bakke O, Dobberstein B (1990) MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell 63:707–716CrossRefGoogle Scholar
  3. Benveniste EN, Vidovic M, Panek RB, Norris JG, Reddy AT, Benos DJ (1991) Interferon-gamma-induced astrocyte class II major histocompatibility complex gene expression is associated with both protein kinase C activation and Na+ entry. J Biol Chem 266:18119–18126Google Scholar
  4. Bijlmakers ME, Benaroch P, Ploegh HL (1994) Mapping functional regions in the luminal domain of the class II-associated invariant chain. J Exp Med 180:623–625CrossRefGoogle Scholar
  5. Bikoff EK, Kenty G, Van Kaer L (1998) Distinct peptide loading pathways for MHC class II molecules associated with alternative Ii chain isoforms. J Immunol 160:3101–3010Google Scholar
  6. Braunstein D (2004) Functional characterization of class II-associated invariant chains in rainbow trout (Oncorhynchus mykiss). University of Waterloo, MSc Thesis, Waterloo, ONGoogle Scholar
  7. Bremnes B, Madsen T, Gedde-Dahl M, Bakke O (1994) An LI and ML motif in the cytoplasmic tail of the MHC-associated invariant chain mediate rapid internalization. J Cell Sci 107:2021–2032Google Scholar
  8. Cho JY, Skubitz KM, Katz DR, Chain BM (2003) CD98-dependent homotypic aggregation is associated with translocation of protein kinase Cδ and activation of mitogen-activated protein kinases. Exp Cell Res 286:1–11CrossRefGoogle Scholar
  9. Christie D (2007) Regulation of MH class II associated invariant chain in Oncorhynchus mykiss. University of Waterloo, MSc Thesis, Waterloo, ONGoogle Scholar
  10. Corripio-Miyar Y, Bird S, Tsamopoulos K, Secombes CJ (2007) Cloning and expression analysis of two pro-inflammatory cytokines, IL-1β and IL-8, in haddock (Melanogrammus aeglefinus). Mol Immunol 44:1361–1373CrossRefGoogle Scholar
  11. Denzin LK, Hammond C, Cresswell P (1996) HLA-DM interactions with intermediates in HLA-DR maturation and a role for HLA-DM in stabilizing empty HLA-DR molecules. J Exp Med 184:2153–2165CrossRefGoogle Scholar
  12. Dewitte-Orr SJ, Hsu HC, Bols NC (2007) Induction of homotypic aggregation in the rainbow trout macrophage-like cell line, RTS11. Fish Shellfish Immunol 22:487–497CrossRefGoogle Scholar
  13. Dijkstra JM, Kiryu I, Kollner B, Yoshiura Y, Ototake M (2003) MHC class II invariant chain homologues in rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol 15:91–105CrossRefGoogle Scholar
  14. Dijkstra JM, Grimholt U, Leong J, Koop BF, Hashimoto K (2013) Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large group of vertebrates. BMC Evol Biol 13:260.  https://doi.org/10.1186/1471-2148-13-260 CrossRefGoogle Scholar
  15. Dixon B (2012) Vaccines for finfish aquaculture: what do we need to know to make them work? Electron J Biotechnol 15(5).  https://doi.org/10.2225/vol15-issue5-fulltext-18
  16. Dixon B, Stet RJM (2001) The relationship between major histocompatibility receptors and innate immunity in teleost fish. Dev Comp Immunol 25:683–699CrossRefGoogle Scholar
  17. Dower NA, Stang SL, Bottorff DA, Ebinu JO, Dickie P, Ostergaard HL, Stone JC (2000) RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat Immunol 1:317–321CrossRefGoogle Scholar
  18. Downward J, Graves JD, Warne PH, Rayter S, Cantrell DA (1990) Stimulation of p21ras upon T-cell activation. Nature 346:719–723CrossRefGoogle Scholar
  19. Dzietko M, Hahnemann M, Polley O, Sifringer M, Felderhoff-Mueser U, Buhrer C (2015) Effects of PMA (Phorbol-12-myristate-13-acetate) on the developing rodent brain. Biomed Res Int 2015:1–9.  https://doi.org/10.1155/2015/318306 CrossRefGoogle Scholar
  20. Eichelbaum K, Krijgsveld J (2014) Rapid temporal dynamics of transcription, protein synthesis and secretion during macrophage activation. Mol Cell Proteomics 13:792–810CrossRefGoogle Scholar
  21. Eichmann TO, Lass A (2015) DAG tales: the multiple faces of diacylglycerol – stereochemistry, metabolism, and signaling. Cell Mol Life Sci 72:3931–3952CrossRefGoogle Scholar
  22. Fortin J, Cloutier M, Thibodeau J (2013) Exposing the specific roles of the invariant chain isoforms in shaping the MHC class II peptidome. Front Immunol 4.  https://doi.org/10.3389/fimmu.2013.00443
  23. Fujiki K, Smith CM, Liu L, Sundick RS, Dixon B (2003) Alternate forms of MHC class II-associated invariant chain are not produced by alternative splicing in rainbow trout (Oncorhynchus mykiss) but are encoded by separate genes. Dev Comp Immunol 27:377–391CrossRefGoogle Scholar
  24. Ganassin RC, Bols NC (1998) Development of a monocyte/macrophage-like cell line, RTS11, from rainbow trout spleen. Fish Shellfish Immunol 8:457–476CrossRefGoogle Scholar
  25. Gedde-Dahl M, Freisewinkel I, Staschewski M, Schenck K, Koch N, Bakke O (1997) Exon 6 is essential for invariant chain trimerization and induction of large endosomal structures. J Biol Chem 272:8281–8287CrossRefGoogle Scholar
  26. Geneve L, Chemali M, Desjardins M, Labrecque N, Thibodeau J (2012) Human invariant chain isoform p35 restores thymic selection and antigen presentation in CD74-deficient mice. Immunol Cell Biol 90:896–902CrossRefGoogle Scholar
  27. Gordon JR, Galli SJ (1990) Phorbol 12-Myristate 13-acetate-induced development of functionally active mast cells in W/Wv but not SI/SId genetically mast cell-deficient mice. Blood 75:1637–1645Google Scholar
  28. Haghighi M, Sharif Rohani M, Pourmoghim H, Samadi M, Tavoli M, Eslami M, Yusefi R (2017) Enhancement of immune responses of rainbow trout (Oncorhynchus mykiss) fed a diet supplemented with Aloe vera extract. Iran J Fish Sci 16:884–896Google Scholar
  29. Hirono I, Nam BH, Kurobe T, Aoki T (2000) Molecular cloning, characterization, and expression of TNF cDNA and gene from Japanese flounder Paralychthys olivaceus. J Immunol 165:4423–4427CrossRefGoogle Scholar
  30. Iliev DB, Liarte CQ, MacKenzie S, Goetz FW (2005) Activation of rainbow trout (Oncorhynchus mykiss) mononuclear phagocytes by different pathogen associated molecular pattern (PAMP) bearing agents. Mol Immunol 41:1215–1223CrossRefGoogle Scholar
  31. Kales SC (2006) A functional study of major histocompatibility expression and immune function in rainbow trout, (Oncorhynchus mykiss). PhD Thesis, Waterloo, ON: University of WaterlooGoogle Scholar
  32. Kales SC, Bols NC, Dixon B (2007) Calreticulin in rainbow trout: a limited response to ER stress. Comp Biochem Physiol B 147:607–615CrossRefGoogle Scholar
  33. Kampgen E, Koch N, Koch F, Stoger P, Heufler C, Schuler G, Romani N (1991) Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc Natl Acad Sci USA 88:3014–3018CrossRefGoogle Scholar
  34. Kling P, Modig C, Mujahed H, Khalaf H, von Hofsten J, Olssen P (2013) Differential regulation of the rainbow trout (Oncorhynchus mykiss) MT-A gene by nuclear factor interleukin-6 and activator protein-1. BMC Mol Biol 14:28.  https://doi.org/10.1186/1471-2199-14-28 CrossRefGoogle Scholar
  35. Koch N (1988) Posttranslational modifications of the Ia-associated invariant protein p41 after gene transfer. Biochemistry 27:4097–4102CrossRefGoogle Scholar
  36. Lamb CA, Cresswell P (1992) Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes. J Immunol 148:3478–3482Google Scholar
  37. Landsverk OJB, Bakke O, Gregers TF (2009) MHC II and the endocytic pathways: regulation by invariant chain. Scand J Immunol 70:184–193CrossRefGoogle Scholar
  38. Li X, Du H, Liu L, You X, Wu M, Liao Z (2017) MHC class II alpha, beta and MHC class II-associated invariant chains from Chinese sturgeon (Acipenser sinensis) and their response to immune stimulation. Fish Shellfish Immunol 70:1–12CrossRefGoogle Scholar
  39. Liu T, Zhang L, Joo D, Sun S-C (2017) NF-κB signaling in inflammation. Signal Transduction Targeted Ther 2.  https://doi.org/10.1038/sigtrans.2017.23
  40. Machamer CE, Cresswell P (1982) Biosynthesis and glycosylation of the invariant chain associated with HLA-DR antigens. J Immunol 129:2564–2569Google Scholar
  41. Majewski M, Bose TO, Sille FCM, Pollington AM, Fiebiger E, Boes M (2007) Protein kinase C delta stimulates antigen presentation by class II MHC in murine dendritic cells. Int Immunol 19:719–732CrossRefGoogle Scholar
  42. Marks MS, Blum JS, Cresswell P (1990) Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens. J Cell Biol 111:839–855CrossRefGoogle Scholar
  43. Mihelic M, Dobersek A, Guncar G, Turk D (2008) Inhibitory fragment from the p41 form of invariant chain can regulate activity of cysteine cathepsins in antigen presentation. J Biol Chem 283:14453–14460CrossRefGoogle Scholar
  44. Monjo AL, Poynter SJ, DeWitte-Orr SJ (2017) CHSE-214: a model for studying extracellular dsRNA sensing in vitro. Fish Shellfish Immunol 68:266–271CrossRefGoogle Scholar
  45. Nagelkerke LAJ, Pannevis MC, Houlihan DF, Secombes CJ (1990) Oxygen uptake of rainbow trout Oncorhynchus mykiss phagocytes following stimulation of the respiratory burst. J Exp Biol 154:339–353Google Scholar
  46. Neefjes J, Longsma MLM, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11:823–836CrossRefGoogle Scholar
  47. Newton AC (1995) Protein kinase C: structure function, and regulation. J Biol Chem 270:28495–28498CrossRefGoogle Scholar
  48. Newton AC (2009) Protein kinase C: poised to signal. Am J Physiol Endocrinol Metab 298:E395–E402CrossRefGoogle Scholar
  49. O’Sullivan DM, Noonan D, Quaranta V (1987) Four Ia invariant chain forms drive from a single gene by alternative splicing and alternate initiation of transcription/translation. J Exp Med 166:444–460CrossRefGoogle Scholar
  50. Paulnock-King D, Sizer KC, Freund YR, Jones PP, Parnes JR (1985) Coordinate induction of Ia alpha, beta, and Ii mRNA in a macrophage cell line. J Immunol 173:4553–4560Google Scholar
  51. Press CM, Evensen O (1999) The morphology of the immune system in teleost fishes. Fish Shellfish Immunol 9:309–318CrossRefGoogle Scholar
  52. Reid S (2005) Rainbow trout (Oncorhynchus mykiss) invariant chain: characterizing the role of 14-1 in antigen presentation. MSc Thesis Waterloo, ON: University of WaterlooGoogle Scholar
  53. Roche PA, Marks MS, Cresswell P (1991) Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain. Nature 354:392–394CrossRefGoogle Scholar
  54. Romagnoli P, Germain RN (1994) The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy. J Exp Med 180:1107–1113CrossRefGoogle Scholar
  55. Schroder B (2016) The multifaceted roles of the invariant chain CD74 – more than justa chaperone. Biochim Biophys Acta 1863:1269–1281CrossRefGoogle Scholar
  56. Semple SL, Vo NTK, Li AR, Pham PH, Bols NC, Dixon B (2017) Development and use of an Arctic charr cell line to study antiviral responses at extremely low temperatures. J Fish Dis 40:1423–1439CrossRefGoogle Scholar
  57. Semple SL, Kellendon CK, Al-Hussinee L, MacInnes JI, Lumsden JS, Dixon B (2018a) Serum IgM, MH class IIβ genotype and respiratory burst activity do not differ between rainbow trout families displaying resistance or susceptibility to the coldwater pathogen, Flavobacterium psychrophilum. Aquaculture 483:131–140CrossRefGoogle Scholar
  58. Semple SL, Vo NTK, Poynter SJ, Li M, Heath DD, DeWitte-Orr SJ, Dixon B (2018b) Extracellular dsRNA induces a type I interferon response mediated via class A scavenger receptors in a novel Chinook salmon derived spleen cell line. Dev Comp Immunol 89:93–101CrossRefGoogle Scholar
  59. Semple SL, Mulder IM, Rodriguez-Ramos T, Power M, Dixon B (2018c) Long-term implantation of acoustic transmitters induces chronic inflammatory cytokine expression in adult rainbow trout (Oncorhynchus mykiss). Vet Immunol Immunopathol 205:1–9Google Scholar
  60. Sever L, Bols NC, Dixon B (2013) The cloning and inducible expression of the rainbow trout ERp57 gene. Fish Shellfish Immunol 34:410–429CrossRefGoogle Scholar
  61. Sever L, Vo NTK, Bols NC, Dixon B (2014) Expression of tapasin in rainbow trout tissues and cell lines and up regulation in a monocyte/macrophage cell line (RTS11) by a viral mimic and viral infection. Dev Comp Immunol 44:86–93CrossRefGoogle Scholar
  62. Sever L, Vo NTK, Bols NC, Dixon B (2018) Tapasin’s protein interactions in the rainbow trout peptide-loading complex. Dev Comp Immunol 81:262–270CrossRefGoogle Scholar
  63. Simonis S, Cullen SE (1986) Fatty acylation of murine Ia alpha, beta and invariant chains. J Immunol 136:2962–2967Google Scholar
  64. Singh BK, Kambayashi T (2016) The immunomodulatory functions of diacylglycerol kinase ζ. Front Cell Dev Biol 4.  https://doi.org/10.3389/fcell.2016.00096
  65. Sloan VS, Cameron P, Porter G, Gammon M, Amaya M, Mellins E, Zaller DM (1995) Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375:802–806CrossRefGoogle Scholar
  66. Spiro RC, Quaranta V (1989) The invariant chain is a phosphorylated subunit of class II molecules. J Immunol 143:2589–2594Google Scholar
  67. Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrom M, Gregers TF et al (2011) The genome sequence of Atlantic cod reveals a unique immune system. Nature 477:207–210CrossRefGoogle Scholar
  68. Stet RJ, Kruiswijk CP, Dixon B (2003) Major histocompatibility lineages and immune gene function in teleost fishes: the road not taken. Crit Rev Immunol 23:441–471CrossRefGoogle Scholar
  69. Stillwell W (2016) An introduction to biological membranes. Elsevier Science, New YorkGoogle Scholar
  70. Strubin M, Berte C, Mach B (1986a) Alternative splicing and alternative initiation of translation explain the four forms of the Ia antigen-associated invariant chain. EMBO J 5:3483–3488CrossRefGoogle Scholar
  71. Strubin M, Long EO, Mach B (1986b) Two forms of the Ia antigen-associated invariant chain result from alternative initiations at two in-phase AUGs. Cell 47:619–625CrossRefGoogle Scholar
  72. Stumptner-Cuvelette P, Benaroch P (2002) Multiple roles of the invariant chain in MHC class II function. Biochim Biophys Acta 1542:1–13CrossRefGoogle Scholar
  73. Takashiba S, Van Dyke TE, Amar S, Murayama Y, Soskolne AW, Shapira L (1999) Differentiation of monocytes to macrophages primes cells for lipopolysaccharide stimulation via accumulation of cytoplasmic nuclear factor κΒ. Infect Immun 67:5573–5578Google Scholar
  74. Thelemann C, Eren RO, Coutaz M, Brasseit J, Bouzourene H, Rosa M, Duval A, Lavanchy C, Mack V, Mueller C, Reith W, Acha-Orbea H (2014) Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis. PLoS One 9:e86844CrossRefGoogle Scholar
  75. Tsuchiya S, Kobayashi Y, Goto Y, Okumura H, Nakae S, Konno T, Tada K (1982) Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res 42:1530–1536Google Scholar
  76. Vogt AB, Kropshofer H, Moldenhauer G, Hammerling GJ (1996) Kinetic analysis of peptide loading onto HLA-DR molecules mediated by HLA-DM. Proc Natl Acad Sci USA 93:9724–9729CrossRefGoogle Scholar
  77. Yamamoto K, Koch N, Steinmetz M, Hammerling GJ (1985) One gene encodes two distinct Ia-associated invariant chains. J Immunol 134:3461–3467Google Scholar
  78. Yamauchi Y, Kuroki M, Imakiire T, Uno K, Abe H, Beppu R, Yamashita Y, Kuroki M, Shirakusa T (2002) Opposite effects of thrombospondin-1 via CD36 and CD47 on homotypic aggregation of monocytic cells. Matrix Biol 21:441–448CrossRefGoogle Scholar
  79. Yoder JA, Haire RN, Litman GW (1999) Cloning of two zebrafish cDNAs that share domains with the MHC class II-associated invariant chain. Immunogenetics 50:84–88CrossRefGoogle Scholar
  80. Zapata AG, Torroba M, Alvarez F, Anderson DP, Dixon OW, Misniewski M (1987) Electron microscopic examination of antigen uptake by salmonid gill cells after bath immunization with a bacterin. J Fish Biol 31:209–217CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of BiologyUniversity of WaterlooWaterlooCanada

Personalised recommendations