Advertisement

An Ancestral Immune Surveillance System in the Amphibian Xenopus Connecting Certain Heat Shock Proteins with Classical and Nonclassical MHC Class I Molecules

  • Jacques Robert
  • Maureen Banach
  • Eva-Stina Edholm
Chapter

Abstract

Studies in the amphibian Xenopus, a vertebrate species that diverged from a common ancestor with mouse and human more than 350 million years ago, provide evolutionary insights into the convergent roles of certain hsps such as gp96 and HSP70 as well as classical and nonclassical MHC class I molecules in cancer immune surveillance. Evidence that in Xenopus gp96 and HSP70 can elicit potent antitumor responses dependent on antigen representation by nonclassical MHC class Ib molecules and presumably involving innate T cells suggests the existence of an ancestral immune surveillance system in antigen-presenting cells such as macrophages integrating hsps with classical and nonclassical MHC molecules. The particular connection revealed in Xenopus between hsps and nonclassical MHC molecules presenting conserved patterns to innate T cells affords new avenues to develop therapeutic strategies against cancer.

Keywords

Comparative immunology Innate T cells Tumor immunity Evolution Unconventional T cells 

Notes

Acknowledgments

We would like to thank Dr. Edith Lord for critical reading of the manuscript. This work was supported by a R24-AI-059830 grant from the National Institute of Allergy and Infectious Diseases (NIH/NIAID) and from the Kesel Fund of Rochester Area Community Foundation, Rochester, NY. M.B. was supported by a predoctoral fellowship Ruth L. Kirschstein Predoctoral F31 (F31CA192664) from the National Cancer Institute (NIH/NCI). E-S.E. was supported by the National Science Foundation IOS-1456213 and a 2015 Career in Immunology Fellowship from the American Association of Immunologists.

References

  1. 1.
    Hendrick JP, Hartl FU (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62:349–384CrossRefGoogle Scholar
  2. 2.
    Calderwood SK, Gong J (2016) Heat shock proteins promote cancer: it’s a protection racket. Trends Biochem Sci 41:311CrossRefGoogle Scholar
  3. 3.
    Srivastava P (2002a) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20:395–425CrossRefGoogle Scholar
  4. 4.
    Srivastava P (2002b) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2:185–194CrossRefGoogle Scholar
  5. 5.
    Bendz H, Ruhland SC, Pandya MJ, Hainzl O, Riegelsberger S, Brauchle C, Mayer MP, Buchner J, Issels RD, Noessner E (2007) Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling. J Biol Chem 282:31688–31702CrossRefGoogle Scholar
  6. 6.
    Blachere NE, Li Z, Chandawarkar RY, Suto R, Jaikaria NS, Basu S, Udono H, Srivastava PK (1997) Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med 186:1315–1322CrossRefGoogle Scholar
  7. 7.
    Suto R, Srivastava PK (1995) A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585–1588CrossRefGoogle Scholar
  8. 8.
    Robert J, Gantress J, Rau L, Bell A, Cohen N (2002) Minor histocompatibility antigen-specific MHC-restricted CD8 T cell responses elicited by heat shock proteins. J Immunol 168:1697–1703CrossRefGoogle Scholar
  9. 9.
    Robert J, Menoret A, Basu S, Cohen N, Srivastava PR (2001) Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70. Eur J Immunol 31:186–195CrossRefGoogle Scholar
  10. 10.
    Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313CrossRefGoogle Scholar
  11. 11.
    Binder RJ, Han DK, Srivastava PK (2000) CD91: a receptor for heat shock protein gp96. Nat Immunol 1:151–155CrossRefGoogle Scholar
  12. 12.
    Binder RJ, Srivastava PK (2005) Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells. Nat Immunol 6:593–599CrossRefGoogle Scholar
  13. 13.
    Lammert E, Arnold D, Nijenhuis M, Momburg F, Hammerling GJ, Brunner J, Stevanovic S, Rammensee HG, Schild H (1997) The endoplasmic reticulum-resident stress protein gp96 binds peptides translocated by TAP. Eur J Immunol 27:923–927CrossRefGoogle Scholar
  14. 14.
    Adams EJ, Luoma AM (2013) The adaptable major histocompatibility complex (MHC) fold: structure and function of nonclassical and MHC class I-like molecules. Annu Rev Immunol 31:529–561CrossRefGoogle Scholar
  15. 15.
    Edholm ES, Grayfer L, Robert J (2014b) Evolution of nonclassical MHC-dependent invariant T cells. Cell Mol Life Sci 71:4763–4780CrossRefGoogle Scholar
  16. 16.
    Gleimer M, Parham P (2003) Stress management: MHC class I and class I-like molecules as reporters of cellular stress. Immunity 19:469–477CrossRefGoogle Scholar
  17. 17.
    Gomes AQ, Correia DV, Silva-Santos B (2007) Non-classical major histocompatibility complex proteins as determinants of tumour immunosurveillance. EMBO Rep 8:1024–1030CrossRefGoogle Scholar
  18. 18.
    Robert J, Goyos A, Nedelkovska H (2009) Xenopus, a unique comparative model to explore the role of certain heat shock proteins and non-classical MHC class Ib gene products in immune surveillance. Immunol Res 45:114CrossRefGoogle Scholar
  19. 19.
    Robert J, Ohta Y (2009) Comparative and developmental study of the immune system in Xenopus. Dev Dyn 238:1249–1270CrossRefGoogle Scholar
  20. 20.
    Flajnik MF, Du Pasquier L (1990) The major histocompatibility complex of frogs. Immunol Rev 113:47–63CrossRefGoogle Scholar
  21. 21.
    Flajnik MF, Kaufman JF, Hsu E, Manes M, Parisot R, Du Pasquier L (1986) Major histocompatibility complex-encoded class I molecules are absent in immunologically competent Xenopus before metamorphosis. J Immunol 137:3891–3899PubMedGoogle Scholar
  22. 22.
    Kau CL, Turpen JB (1983) Dual contribution of embryonic ventral blood island and dorsal lateral plate mesoderm during ontogeny of hemopoietic cells in Xenopus laevis. J Immunol 131:2262–2266PubMedGoogle Scholar
  23. 23.
    Du Pasquier L, Weiss N (1973) The thymus during the ontogeny of the toad Xenopus laevis: growth, membrane-bound immunoglobulins and mixed lymphocyte reaction. Eur J Immunol 3:773–777CrossRefGoogle Scholar
  24. 24.
    Bechtold TE, Smith PB, Turpen JB (1992) Differential stem cell contributions to thymocyte succession during development of Xenopus laevis. J Immunol 148:2975–2982PubMedGoogle Scholar
  25. 25.
    Turpen JB, Smith PB (1989) Precursor immigration and thymocyte succession during larval development and metamorphosis in Xenopus. J Immunol 142:41–47PubMedGoogle Scholar
  26. 26.
    Flajnik MF, Du Pasquier L (1988) MHC class I antigens as surface markers of adult erythrocytes during the metamorphosis of Xenopus. Dev Biol 128:198–206CrossRefGoogle Scholar
  27. 27.
    Rollins-Smith LA, Flajnik MF, Blair PJ, Davis AT, Green WF (1997) Involvement of thyroid hormones in the expression of MHC class I antigens during ontogeny in Xenopus. Dev Immunol 5:133–144CrossRefGoogle Scholar
  28. 28.
    Salter-Cid L, Nonaka M, Flajnik MF (1998) Expression of MHC class Ia and class Ib during ontogeny: high expression in epithelia and coregulation of class Ia and lmp7 genes. J Immunol 160:2853–2861PubMedGoogle Scholar
  29. 29.
    Du Pasquier L, Schwager J, Flajnik MF (1989) The immune system of Xenopus. Annu Rev Immunol 7:251–275CrossRefGoogle Scholar
  30. 30.
    Goyos A, Robert J (2009) Tumorigenesis and anti-tumor immune responses in Xenopus. Front Biosci 14:167–176CrossRefGoogle Scholar
  31. 31.
    Du Pasquier L, Robert J (1992) In vitro growth of thymic tumor cell lines from Xenopus. Dev Immunol 2:295–307CrossRefGoogle Scholar
  32. 32.
    Robert J, Guiet C, Du Pasquier L (1994) Lymphoid tumors of Xenopus laevis with different capacities for growth in larvae and adults. Dev Immunol 3:297–307CrossRefGoogle Scholar
  33. 33.
    Earley EM, Reinschmidt DC, Tompkins R, Gebhardt BM (1995) Tissue culture of a mixed cell thymic tumor from Xenopus laevis. In Vitro Cell Dev Biol Anim 31:255–257CrossRefGoogle Scholar
  34. 34.
    Du Pasquier L, Wilson M, Sammut B (2009) The fate of duplicated immunity genes in the dodecaploid Xenopus ruwenzoriensis. Front Biosci 14:177–191CrossRefGoogle Scholar
  35. 35.
    Robert J, Guiet C, Du Pasquier L (1995) Ontogeny of the alloimmune response against a transplanted tumor in Xenopus laevis. Differentiation 59:135–144CrossRefGoogle Scholar
  36. 36.
    Du Pasquier L, Courtet M, Robert J (1995) A Xenopus lymphoid tumor cell line with complete Ig genes rearrangements and T-cell characteristics. Mol Immunol 32:583–593CrossRefGoogle Scholar
  37. 37.
    Chretien I, Robert J, Marcuz A, Garcia-Sanz JA, Courtet M, Du Pasquier L (1996) CTX, a novel molecule specifically expressed on the surface of cortical thymocytes in Xenopus. Eur J Immunol 26:780–791CrossRefGoogle Scholar
  38. 38.
    Robert J, Cohen N (1999) In vitro differentiation of a CD4/CD8 double-positive equivalent thymocyte subset in adult Xenopus. Int Immunol 11:499–508CrossRefGoogle Scholar
  39. 39.
    Goyos A, Ohta Y, Guselnikov S, Robert J (2009) Novel nonclassical MHC class Ib genes associated with CD8 T cell development and thymic tumors. Mol Immunol 46:1775–1786CrossRefGoogle Scholar
  40. 40.
    Robert J, Guiet C, Cohen N, Du Pasquier L (1997) Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis. Int J Cancer 70:330–334CrossRefGoogle Scholar
  41. 41.
    Goyos A, Cohen N, Gantress J, Robert J (2004) Anti-tumor MHC class Ia-unrestricted CD8 T cell cytotoxicity elicited by the heat shock protein gp96. Eur J Immunol 34:2449–2458CrossRefGoogle Scholar
  42. 42.
    Horton TL, Minter R, Stewart R, Ritchie P, Watson MD, Horton JD (2000) Xenopus NK cells identified by novel monoclonal antibodies. Eur J Immunol 30:604–613CrossRefGoogle Scholar
  43. 43.
    Rau L, Gantress J, Bell A, Stewart R, Horton T, Cohen N, Horton J, Robert J (2002) Identification and characterization of Xenopus CD8+ T cells expressing an NK cell-associated molecule. Eur J Immunol 32:1574–1583CrossRefGoogle Scholar
  44. 44.
    Horton TL, Stewart R, Cohen N, Rau L, Ritchie P, Watson MD, Robert J, Horton JD (2003) Ontogeny of Xenopus NK cells in the absence of MHC class I antigens. Dev Comp Immunol 27:715–726CrossRefGoogle Scholar
  45. 45.
    Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17:353–362CrossRefGoogle Scholar
  46. 46.
    Facciponte JG, Wang XY, Subjeck JR (2007) Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I. Eur J Immunol 37:2268–2279CrossRefGoogle Scholar
  47. 47.
    Murshid A, Borges TJ, Calderwood SK (2015) Emerging roles for scavenger receptor SREC-I in immunity. Cytokine 75:256–260CrossRefGoogle Scholar
  48. 48.
    Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034CrossRefGoogle Scholar
  49. 49.
    Warger T, Hilf N, Rechtsteiner G, Haselmayer P, Carrick DM, Jonuleit H, von Landenberg P, Rammensee HG, Nicchitta CV, Radsak MP, Schild H (2006) Interaction of TLR2 and TLR4 ligands with the N-terminal domain of Gp96 amplifies innate and adaptive immune responses. J Biol Chem 281:22545–22553CrossRefGoogle Scholar
  50. 50.
    Nedelkovska H, Robert J (2013) Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis. Cancer Immun 13:4PubMedPubMedCentralGoogle Scholar
  51. 51.
    Robert J, Ramanayake T, Maniero GD, Morales H, Chida AS (2008) Phylogenetic conservation of glycoprotein 96 ability to interact with CD91 and facilitate antigen cross-presentation. J Immunol 180:3176–3182CrossRefGoogle Scholar
  52. 52.
    Callahan MK, Chaillot D, Jacquin C, Clark PR, Menoret A (2002) Differential acquisition of antigenic peptides by Hsp70 and Hsc70 under oxidative conditions. J Biol Chem 277:33604–33609CrossRefGoogle Scholar
  53. 53.
    Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715–727CrossRefGoogle Scholar
  54. 54.
    Benevolo M, Mottolese M, Tremante E, Rollo F, Diodoro MG, Ercolani C, Sperduti I, Lo Monaco E, Cosimelli M, Giacomini P (2011) High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis. J Transl Med 9:184CrossRefGoogle Scholar
  55. 55.
    de Kruijf EM, Sajet A, van Nes JG, Natanov R, Putter H, Smit VT, Liefers GJ, van den Elsen PJ, van de Velde CJ, Kuppen PJ (2010) HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol 185:7452–7459CrossRefGoogle Scholar
  56. 56.
    He X, Dong DD, Yie SM, Yang H, Cao M, Ye SR, Li K, Liu J, Chen J (2010) HLA-G expression in human breast cancer: implications for diagnosis and prognosis, and effect on allocytotoxic lymphocyte response after hormone treatment in vitro. Ann Surg Oncol 17:1459–1469CrossRefGoogle Scholar
  57. 57.
    Ye SR, Yang H, Li K, Dong DD, Lin XM, Yie SM (2007) Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer. Mod Pathol 20:375–383CrossRefGoogle Scholar
  58. 58.
    Yie SM, Yang H, Ye SR, Li K, Dong DD, Lin XM (2007) Expression of HLA-G is associated with prognosis in esophageal squamous cell carcinoma. Am J Clin Pathol 128:1002–1009CrossRefGoogle Scholar
  59. 59.
    McEwen-Smith RM, Salio M, Cerundolo V (2015) The regulatory role of invariant NKT cells in tumor immunity. Cancer Immunol Res 3:425–435CrossRefGoogle Scholar
  60. 60.
    Robertson FC, Berzofsky JA, Terabe M (2014) NKT cell networks in the regulation of tumor immunity. Front Immunol 5:543CrossRefGoogle Scholar
  61. 61.
    Nagato K, Motohashi S, Ishibashi F, Okita K, Yamasaki K, Moriya Y, Hoshino H, Yoshida S, Hanaoka H, Fujii S, Taniguchi M, Yoshino I, Nakayama T (2012) Accumulation of activated invariant natural killer T cells in the tumor microenvironment after alpha-galactosylceramide-pulsed antigen presenting cells. J Clin Immunol 32:1071–1081CrossRefGoogle Scholar
  62. 62.
    Altman JB, Benavides AD, Das R, Bassiri H (2015) Antitumor responses of invariant natural killer T cells. J Immunol Res 2015:652875CrossRefGoogle Scholar
  63. 63.
    Flajnik MF, Kasahara M (2001) Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15:351–362CrossRefGoogle Scholar
  64. 64.
    Yeager M, Kumar S, Hughes AL (1997) Sequence convergence in the peptide-binding region of primate and rodent MHC class Ib molecules. Mol Biol Evol 14:1035–1041CrossRefGoogle Scholar
  65. 65.
    Brossay L, Chioda M, Burdin N, Koezuka Y, Casorati G, Dellabona P, Kronenberg M (1998) CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 188:1521–1528CrossRefGoogle Scholar
  66. 66.
    Dascher CC (2007) Evolutionary biology of CD1. Curr Top Microbiol Immunol 314:3–26PubMedGoogle Scholar
  67. 67.
    Miller MM, Wang C, Parisini E, Coletta RD, Goto RM, Lee SY, Barral DC, Townes M, Roura-Mir C, Ford HL, Brenner MB, Dascher CC (2005) Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc Natl Acad Sci U S A 102:8674–8679CrossRefGoogle Scholar
  68. 68.
    Salomonsen J, Sorensen MR, Marston DA, Rogers SL, Collen T, van Hateren A, Smith AL, Beal RK, Skjodt K, Kaufman J (2005) Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc Natl Acad Sci U S A 102:8668–8673CrossRefGoogle Scholar
  69. 69.
    Yang Z, Wang C, Wang T, Bai J, Zhao Y, Liu X, Ma Q, Wu X, Guo Y, Zhao Y, Ren L (2015) Analysis of the reptile CD1 genes: evolutionary implications. Immunogenetics 67:337–346CrossRefGoogle Scholar
  70. 70.
    Edholm ES, Goyos A, Taran J, De Jesus Andino F, Ohta Y, Robert J (2014a) Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae. Immunogenetics 66:411–426CrossRefGoogle Scholar
  71. 71.
    Flajnik MF, Kasahara M, Shum BP, Salter-Cid L, Taylor E, Du Pasquier L (1993) A novel type of class I gene organization in vertebrates: a large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus. EMBO J 12:4385–4396PubMedPubMedCentralGoogle Scholar
  72. 72.
    Goyos A, Sowa J, Ohta Y, Robert J (2011) Remarkable conservation of distinct nonclassical MHC class I lineages in divergent amphibian species. J Immunol 186:372–381CrossRefGoogle Scholar
  73. 73.
    Evans BJ (2008) Genome evolution and speciation genetics of clawed frogs (Xenopus and Silurana). Front Biosci 13:4687–4706CrossRefGoogle Scholar
  74. 74.
    Goyos A, Guselnikov S, Chida AS, Sniderhan LF, Maggirwar SB, Nedelkovska H, Robert J (2007) Involvement of nonclassical MHC class Ib molecules in heat shock protein-mediated anti-tumor responses. Eur J Immunol 37:1494–1501CrossRefGoogle Scholar
  75. 75.
    Haynes-Gilmore N, Banach M, Edholm ES, Lord E, Robert J (2014) A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model. Carcinogenesis 35:1807–1813CrossRefGoogle Scholar
  76. 76.
    Bassiri H, Das R, Guan P, Barrett DM, Brennan PJ, Banerjee PP, Wiener SJ, Orange JS, Brenner MB, Grupp SA, Nichols KE (2014) iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo. Cancer Immunol Res 2:59–69CrossRefGoogle Scholar
  77. 77.
    Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13:101–117CrossRefGoogle Scholar
  78. 78.
    Pilones KA, Aryankalayil J, Babb JS, Demaria S (2014) Invariant natural killer T cells regulate anti-tumor immunity by controlling the population of dendritic cells in tumor and draining lymph nodes. J Immunother Cancer 2:37CrossRefGoogle Scholar
  79. 79.
    Pilones KA, Aryankalayil J, Demaria S (2012) Invariant NKT cells as novel targets for immunotherapy in solid tumors. Clin Dev Immunol 2012:720803CrossRefGoogle Scholar
  80. 80.
    Kronenberg M (2005) Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23:877–900CrossRefGoogle Scholar
  81. 81.
    Matsuda JL, Mallevaey T, Scott-Browne J, Gapin L (2008) CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system. Curr Opin Immunol 20(3):358–368. https://doi.org/10.1016/j.coi.2008.03.018. Epub 2008 May 22CrossRefGoogle Scholar
  82. 82.
    Edholm ES, Albertorio Saez LM, Gill AL, Gill SR, Grayfer L, Haynes N, Myers JR, Robert J (2013) Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians. Proc Natl Acad Sci U S A 110:14342–14347CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jacques Robert
    • 1
  • Maureen Banach
    • 1
  • Eva-Stina Edholm
    • 1
  1. 1.Department of Microbiology and ImmunologyUniversity of Rochester Medical CenterRochesterUSA

Personalised recommendations