The RT6 (Art2) family of ADP-ribosyltransferases in rat and mouse

  • Rita Bortell
  • Toshihiro Kanaitsuka
  • Linda A. Stevens
  • Joel Moss
  • John P. Mordes
  • Aldo A. Rossini
  • Dale L. Greiner
Part of the Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease book series (DMCB, volume 30)

Abstract

Recent evidence suggests that a new member of the mono-ADP-ribosyltransferase/NAD glycohydrolase family, RT6, may be important in immune regulation. RT6 is expressed in two allelic forms and is present on post-thymic T cells in the rat. RT6-expressing T cells in the rat may have a regulatory role, a conclusion based on their ability to prevent autoimmune diabetes in the BB rat model of insulin-dependent diabetes mellitus. This observation led to investigation of RT6 at a molecular and biochemical level resulting in the determination that RT6 protein exists as both glycosylated and non-glycosylated glycosylphosphatidylinositol (GPI)-linked cell surface molecules. RT6, like many GPI-linked proteins, can mediate cell signal transduction events associated with T cell activation, and is also present in a soluble form in the circulation. The discovery that RT6 is an NAD glycohydrolase and auto-ADP-ribosyltransferase led to the ongoing investigations into the role that enzymatic activity may have in the immunoregulatory function of rat RT6+ T cells. A homologue of rat RT6, termed Rt6, has been identified in the mouse. Rt6 is predominately an ADP-ribosyltransferase enzyme as determined using simple guanidino compounds (e.g. arginine) as ribose acceptors. Abnormalities in mouse Rt6 mRNA are associated with the expression of autoimmunity. In the present manuscript, we review recent data on RT6/Rt6, and discuss the potential mechanisms by which RT6-expressing cells, and perhaps RT6 protein itself, may mediate immune regulation.

Key words

ART mono-ADP-ribosyltransferase RT6 immune regulation autoimmunity 

Abbreviations

ART

NAD+:arginine ADP-ribosyltransferase

DP-BB rat

diabetes-prone BB rat

DR-BB rat

diabetes-resistant BB rat

GPI

glycosylphosphatidylinositol

IDDM

insulin-dependent diabetes mellitus

IEL

intraepithelial lymphocyte

NOD

non-obese diabetic

PI-PLC

phosphatidylinositol-specific phospholipase C

TcR

T cell receptor

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mordes J, Bortell R, Doukas J, Rigby M, Whalen BJ, Zipris D, Greiner DL, Rossini AA: The BB/Wor rat and the balance hypothesis of autoimmunity. Diabetes/Metab Rev 2: 103–109, 1996Google Scholar
  2. 2.
    Mordes JP, Greiner DL, Rossini AA: Animal models of autoimmune diabetes mellitus. In: D LeRoith, SI Taylor, JM Olefsky (eds). Diabetes Mellitus. A Fundamental and Clinical Text. Lippincott-Raven, Philadelphia, 1996, pp 349–360Google Scholar
  3. 3.
    Prochazka M, Gaskins HR, Leiter EH, Koch-Nolte F, Haag F, Thiele H-G: Chromosomal localization, DNA polymorphism, and expression of Rt-6, the mouse homologue of rat T-lymphocyte differentiation markerRT6. Immunogenetics 33: 152–156, 1991PubMedCrossRefGoogle Scholar
  4. 4.
    Koch-Nolte F, Klein J, Hollmann C, Köhl M, Haag F, Gaskins HR, Leiter E, Thiele H-G: Defects in the structure and expression of the genes for the T cell marker Rt6 in NZW and (NZB × NZW)F1 mice. Int Immunol 7: 883–890, 1995PubMedCrossRefGoogle Scholar
  5. 5.
    Lubaroff DM, Butcher G, De Witt C, Gill TJIII, Gönther E, Howard J, Wonigeit K: Fourth international workshop on alloantigenic systems in the rat. Transplant Proc 15: 1683, 1983Google Scholar
  6. 6.
    Greiner DL, Mordes JP, Angelillo M, Handler ES, Mojcik CF, Nakamura N, Rossini AA: Role of regulatory RT6+ T-cells in the pathogenesis of diabetes mellitus in BB/Wor rats. In: E. Shaffir, A.E. Renold (eds). Frontiers in Diabetes Research: Lessons from Animal Diabetes II. John Libbey, London, 1988, pp 58–67Google Scholar
  7. 7.
    Greiner DL, Goldschneider I, Lubaroff DM: Identification of thymocyte progenitors in hemopoietic tissues of the rat. I. A quantitative assay system for thymocyte regeneration. Thymus 6: 181–199, 1984PubMedGoogle Scholar
  8. 8.
    Rossini AA, Mordes JP, Greiner DL, Nakano K, Appel MC, Handler ES: Spleen cell transfusion in the BB/W rat: Prevention of diabetes, NMC restriction, and long term persistence of transfused cells. J Clin Invest 77: 1399–1401, 1986PubMedCrossRefGoogle Scholar
  9. 9.
    Goldschneider I, Kornschlies KL, Greiner DL: Studies of thymo-cytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors. J Exp Med 163: 1–17, 1986PubMedCrossRefGoogle Scholar
  10. 10.
    Mojcik CF, Greiner DL, Medlock ES, Kornschlies KL, Goldschneider I: Characterization of RT6 bearing rat lymphocytes. I. Ontogeny of the RT6+ subset. Cell Immunol 114: 336–346, 1988PubMedCrossRefGoogle Scholar
  11. 11.
    Mojcik CF, Greiner DL, Goldschneider I: Characterization of RT6-bearing lymphocytes. II. Developmental relationships of RT6− and RT6+ T cells. Develop Immuno 11: 191–201, 1991CrossRefGoogle Scholar
  12. 12.
    Thiele H-G, Koch F, Kashan A: Postnatal distribution profiles of Thy-1+ and RT6+ cells in peripheral lymph nodes of DA rats. Transplant Proc 19: 3157–3160, 1987Google Scholar
  13. 13.
    Mojcik CF, Greiner DL, Medlock ES, Goldschneider I: Development of T cell subsets in the rat expressing the RT−6 alloantigen. Fed Proc 44: (abstr) 1301, 1985Google Scholar
  14. 14.
    Greiner DL, Reynolds CW, Lubaroff DM: Maturation of functional T-lymphocyte subpopulations in the rat. Thymus 4: 77–90, 1982PubMedGoogle Scholar
  15. 15.
    Chen-Woan M, McGregor DD, Harris WV, Greiner DL: Monoclonal antibody analysis of Listeria monocytogenes-induced cytotoxic lymphocytes. Immunology 57: 505–513, 1986PubMedGoogle Scholar
  16. 16.
    Angelillo M, Greiner DL, Crisá L, Kitagawa Y, Heyderman JI, Mordes JP, Rossini AA: RT6+ T cell developmental defects in BB/Wor rats. In: E. Shaffir (ed). Frontiers in Diabetes Research II. Lessons from Animal Diabetes III. Smith-Gordon, Edinburgh, 1990, pp 114–119Google Scholar
  17. 17.
    Takada T, Iida K, Moss J: Expression of NAD glycohydrolase activity by rat mammary adenocarcinoma cells transformed with rat T cell alloantigen RT6.2. J Biol Chem 269: 9420–9423, 1994PubMedGoogle Scholar
  18. 18.
    Koch-Nolte F, Haag F, Kastelein R, Bazan F: Uncovered: the family relationship of a T-cell-membrane protein and bacterial toxins. Immunol Today 17: 402–05, 1996PubMedCrossRefGoogle Scholar
  19. 19.
    Haag F, Koch-Nolte F: The vertebrate gene family of mono(ADP-ribosyl)transferases: Proposal for a unified nomenclature. Adv Exp Med Biol 419: 459–462, 1997PubMedGoogle Scholar
  20. 20.
    Angelillo M, Greiner DL, Mordes JP, Handler ES, Nakamura N, McKeever U, Rossini AA: Absence of RT6+ T cells in diabetes-prone BioBreeding/Worcester rats is due to genetic and cell developmental defects. J Immunol 141: 4146–4151, 1988PubMedGoogle Scholar
  21. 21.
    Thiele H-G, Haag F, Nolte F: Asymmetric expression of RT6.1 and RT6.2 alloantigens in (RT6a × RT6b)F1 rats is due to a pretranslational mechanism. Transplant Proc 25: 2786–2788, 1993PubMedGoogle Scholar
  22. 22.
    Greiner DL, Barton RW, Goldschneider I, Lubaroff DM: Genetic linkage and cell distribution analysis of T cell alloantigens in the rat. J Immunogenet 9: 43–50, 1982PubMedCrossRefGoogle Scholar
  23. 23.
    Koch F, Haag F, Kashan A, Thiele H-G: Primary structure of rat RT6.2, a nonglycosylated phosphatidylinositol-linked surface marker of postthymic T cells. Proc Nati Acad Sci USA 87: 964–967, 1990CrossRefGoogle Scholar
  24. 24.
    Haag F, Koch F, Thiele H-G: Nucleotide and deduced amino acid sequence of the rat T-cell alloantigen RT6.1. Nucleic Acids Res 18: 1047, 1990PubMedCrossRefGoogle Scholar
  25. 25.
    Haag F, Andresen V, Karsten S, Koch-Nolte F, Thiele H-G: Both allelic forms of the rat T cell differentiation marker RT6 display nicotinamide adenine dinucleotide (NAD)-glycohydrolase activity, yet only RT6.2 is capable of automodification upon incubation with NAD. Eur J Immunol 25: 2355–2361, 1995PubMedCrossRefGoogle Scholar
  26. 26.
    Maehama T, Hoshino S, Katada T: Increase in ADP-ribosyltransferase activity of rat T lymphocyte alloantigen RT6.1 by a single amino acid mutation. FEBS Lett 388: 189–191, 1996PubMedCrossRefGoogle Scholar
  27. 27.
    Maehama T, Nishina H, Hoshino S, Kanaho Y, Katada T: NAD+-dependent ADP-ribosylation of T lymphocyte alloantigen RT6.1 reversibly proceeding in intact rat lymphocytes. J Biol Chem 270: 22747–22751, 1995PubMedCrossRefGoogle Scholar
  28. 28.
    Rigby MR, Bortell R, Stevens LA, Moss J, Kanaitsuka T, Shigeta H, Mordes JP, Greiner DL, Rossini AA: Rat RT6.2 and mouse Rt6 locus 1 are NAD+:arginine ADP-ribosyltransferases with auto-ADP-ribosylation activity. J Immunol 156: 4259–1265, 1996PubMedGoogle Scholar
  29. 29.
    Moss J, Stevens LA, Cavanagh E, Okazaki IJ, Bortell R, Kanaitsuka T, Mordes JP, Greiner DL, Rossini AA: Characterization of mouse Rt6.1 NAD:arginine ADP-ribosyltransferase. J Biol Chem 272: 4342–4346, 1997PubMedCrossRefGoogle Scholar
  30. 30.
    Haag FA, Kuhlenbäumer G, Koch-Nolte F, Wingender E, Thiele H-G: Structure of the gene encoding the rat T cell ecto-ADP-ribosyltransferase RT6. J Immunol 157: 2022–2030, 1996PubMedGoogle Scholar
  31. 31.
    Koch F, Thiele H-G, Low MG: Release of the rat T cell alloantigen RT−6.2 from cell membranes by phosphatidylinositol-specific phospholipase C. J Exp Med 164: 1338–1343, 1986PubMedCrossRefGoogle Scholar
  32. 32.
    Crisá L, Sarkar P, Waite DJ, Haag F, Koch-Nolte F, Rajan TV, Mordes JP, Handler ES, Thiele H-G, Rossini AA, Greiner DL: An RT6a gene is transcribed and translated in lymphopenic diabetes-prone BB rats. Diabetes 42: 688–695, 1993PubMedCrossRefGoogle Scholar
  33. 33.
    Crisá L, Greiner DL, Mordes JP, MacDonald RG, Handler ES, Czech W, Rossini AA: Biochemical studies of RT6 alloantigens in BB/Wor and normal rats: Evidence for intact but unexpressed RT6a structural gene in diabetes prone BB rats. Diabetes 39: 1279–1288, 1990PubMedCrossRefGoogle Scholar
  34. 34.
    Waite DJ, Handler ES, Mordes JP, Rossini AA, Greiner DL: The RT6 rat lymphocyte alloantigen circulates in soluble form. Cell Immunol 152: 82–95, 1993PubMedCrossRefGoogle Scholar
  35. 35.
    Schwinzer R, Hedrich HJ, Wonigeit K: T cell differentiation in athymic nude rats (rnu/rnu): Demonstration of a distorted T cell subset structure by flow cytometry analysis. Eur J Immunol 19: 1841–1847, 1989PubMedCrossRefGoogle Scholar
  36. 36.
    Waite DJ, Appel MC, Handler ES, Mordes JP, Rossini AA, Greiner DL: Ontogeny and immunohistochemical localization of thymus dependent and thymus independent RT6+ cells in the rat. Am J Pathol 148: 2043–2056, 1996PubMedGoogle Scholar
  37. 37.
    Woda BA, Padden C, McFadden ML: T helper (TH) cells in the BioBreeding Worcester (BB/Wor) rat are subdivided into distinct subpopulations by the OX22 and RT6 antibodies. Diabetes 37 (Suppl. I): (abstr) 205A, 1988Google Scholar
  38. 38.
    Hunt HD, Lubaroff DM: Interaction of T lymphocyte subpopulations bearing the RT-6 alloantigen. Transplant Proc 17: 1861–1863, 1985Google Scholar
  39. 39.
    Ernst DN, Lubaroff DM: Membrane antigen phenotype of sensitized T lymphocytes mediating tuberculin-delayed hypersensitivity in rats. Cell Immunol 88: 436–452, 1984PubMedCrossRefGoogle Scholar
  40. 40.
    Fowell D, Mason D: Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J Exp Med 177: 627–636, 1993PubMedCrossRefGoogle Scholar
  41. 41.
    Fangmann J, Schwinzer R, Wonigeit K: Unusual phenotype of intestinal intraepithelial lymphocytes in the rat: Predominance of T cell receptor a/b+/CD2− cells and high expression of the RT6 alloantigen. Eur J Immunol 21: 753–760, 1991PubMedCrossRefGoogle Scholar
  42. 42.
    Hosseinzadeh R, Goldschneider I: Recent thymic emigrants in the rat express a unique antigenic phenotype and undergo post-thymic maturation in peripheral lymphoid tissues. J Immunol 150: 1670–1679, 1993PubMedGoogle Scholar
  43. 43.
    Zadeh HH, Greiner DL, Wu DY, Tausche F, Goldschneider I: Ab-normalities in the export and fate of recent thymic emigrants in diabetes-prone BB/W rats. Autoimmunity 24: 35–46, 1996PubMedCrossRefGoogle Scholar
  44. 44.
    Groen H, Klatter FA, Brons NHC, Mesander G, Nieuwenhuis P, Kampinga J: Abnormal thymocyte subset distribution and differential reduction of CD4+ and CD8+ T cell subsets during peripheral maturation in diabetes-prone BioBreeding rats. J Immunol 156: 1269–1275, 1996PubMedGoogle Scholar
  45. 45.
    Groen H, Klatter FA, Brons NHC, Wubbena AS, Nieuwenhuis P, Kampinga J: High-frequency, but reduced absolute numbers of recent thymic migrants among peripheral blood T lymphocytes in diabetes-prone BB rats. Cell Immunol 163: 113–119, 1995PubMedCrossRefGoogle Scholar
  46. 46.
    Koch F, Haag F, Thiele H-G: Nucleotide and deduced amino acid sequence for the mouse homologue of the rat T-cell differentiation marker RT6. Nucleic Acids Res 18: 3636, 1990PubMedCrossRefGoogle Scholar
  47. 47.
    Hollmann C, Haag F, Schlott M, Damaske A, Bertuleit H, Matthes M, Köhl M, Thiele H-G, Koch-Nolte F: Molecular characterization of mouse T-cell ecto-ADP-ribosyltransferase Rt6: Cloning of a second functional gene and identification of the Rt6 gene products. Mol Immunol 33: 807–817, 1996PubMedCrossRefGoogle Scholar
  48. 48.
    Koch-Nolte F, Hollmann C, Köhl M, Haag F, Prochazka M, Leiter EH, Thiele H-G: Molecular polymorphism in the Rt6 genes of laboratory mice correlates with the allotypes of the H1 minor histocompatibility system. Immunogenetics 41: 152–155, 1995PubMedCrossRefGoogle Scholar
  49. 49.
    Kanaitsuka T, Bortell F, Stevens LA, Moss J, Sardinha D, Rajan TV, Zipris D, Mordes JP, Greiner DL, Rossini AA: Expression In BALB/c and C57BL/6 mice of Rt6-1 and Rt6-2 ADP-ribosyltransferases that differ in enzymatic activity: C57BL/6 Rt6-1 is a natural transferase knockout. J Immunol 1997, (in press)Google Scholar
  50. 50.
    Koch-Nolte F, Petersen D, Balasubramanian S, Haag F, Kahlke D, Wilier T, Kastelein R, Bazan F, Thiele H-G: Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine protein mono(ADP-ribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins. J Biol Chem 271: 7686–7693, 1996PubMedCrossRefGoogle Scholar
  51. 51.
    Rossini AA, Mordes JP, Pelletier AM, Like AA: Transfusions of whole blood prevent spontaneous diabetes in the BB/W rat. Science 219: 975–977, 1983PubMedCrossRefGoogle Scholar
  52. 52.
    Rossini AA, Faustman D, Woda BA, Like AA, Szymanski I, Mordes JP: Lymphocyte transfusions prevent diabetes in the Bio-Breeding/ Worcester rat. J Clin Invest 74: 39–46, 1984PubMedCrossRefGoogle Scholar
  53. 53.
    Greiner DL, Handler ES, Nakano K, Mordes JP, Rossini AA: Absence of the RT-6 T cell subset in diabetes-prone BB/W rats. J Immunol 136: 148–151, 1986PubMedGoogle Scholar
  54. 54.
    Mordes JP, Gallina DL, Handler ES, Greiner DL, Nakamura N, Pelletier A, Rossini AA: Transfusions enriched for W3/25+ helper/inducer T lymphocytes prevent spontaneous diabetes in the BB/W rat. Diabetologia 30: 22–26, 1987PubMedCrossRefGoogle Scholar
  55. 55.
    Burstein D, Mordes JP, Greiner DL, Stein D, Nakamura N, Handler ES, Rossini AA: Prevention of diabetes in the BB/Wor rat by a single transfusion of spleen cells: Parameters that affect the degree of protection. Diabetes 38: 24–30, 1989PubMedCrossRefGoogle Scholar
  56. 56.
    Jacob HJ, Pettersson A, Wilson D, Mao Y, Lernmark Å, Lander ES: Genetic dissection of autoimmune type I diabetes in the BB rat. Nature Genet 2: 56–60, 1992PubMedCrossRefGoogle Scholar
  57. 57.
    Butler L, Guberski DL, Like AA: Genetics of diabetes production in the Worcester colony of the BB rat. In: E. Shaffir, A.E. Renold (eds). Frontiers in diabetes research: Lessons from animal diabetes II. John Libbey, London, 1988, pp 74–78Google Scholar
  58. 58.
    Greiner DL, Mordes JP, Handler ES, Angelillo M, Nakamura N, Rossini AA: Depletion of RT6.1+ T lymphocytes induces diabetes in resistant BioBreeding/Worcester (BB/W) rats. J Exp Med 166: 461–75, 1987PubMedCrossRefGoogle Scholar
  59. 59.
    Whalen BJ, Greiner DL, Mordes JP, Rossini AA: Adoptive transfer of autoimmune diabetes mellitus to athymic rats: Synergy of CD4+ and CD8+ T cells and prevention by RT6+T cells. J Autoimmun 7: 819–831, 1994PubMedCrossRefGoogle Scholar
  60. 60.
    Whalen BJ, Rossini AA, Mordes JP, Greiner DL: DR-BB rat thymus contains thymocyte populations predisposed to autoreactivity. Diabetes 44: 963–967, 1995PubMedCrossRefGoogle Scholar
  61. 61.
    Kosuda LL, Wayne A, Nahounou M, Greiner DL, Bigazzi PE: Reduction of the RT6.2+ subset of T lymphocytes in brown Norway rats with mercury-induced renal autoimmunity. Cell Immunol 135: 154–167, 1991PubMedCrossRefGoogle Scholar
  62. 62.
    Leiter EH, Serreze DV, Prochazka M: The genetics and epidemiology of diabetes in NOD mice. Immunol Today 11: 147–149, 1990PubMedCrossRefGoogle Scholar
  63. 63.
    Kroczek RA, Gunter KC, Seligmann B, Shevach EM: Induction of T cell activation by monoclonal anti-Thy-1 antibodies. J Immunol 136: 4379–4384, 1986PubMedGoogle Scholar
  64. 64.
    Hahn AB, Soloski MJ: Anti-Qa-2-induced T cell activation. The parameters of activation, the definition of mitogenic and nonmitogenic antibodies, and the differential effects on CD4+ vs. CD8+ T cells. J Immunol 143: 407–413, 1989PubMedGoogle Scholar
  65. 65.
    Rock KL, Reiser H, Bamezai A, McGrew J, Benacerraf B: The LY-6 locus: A multigene family encoding phosphatidylinositol-anchored membrane proteins concerned with T-cell activation. Immunol. Rev 111 (review): 195–224, 1989PubMedCrossRefGoogle Scholar
  66. 66.
    Rigby M, Bortell R, Greiner DL, Czech MP, Klarlund JK, Mordes JP, Rossini AA: The rat T-cell surface protein RT6 is associated with src family tyrosine kinases and generates an activation signal. Diabetes 45: 1419–1426, 1996PubMedCrossRefGoogle Scholar
  67. 67.
    Hara N, Tsuchiya M, Shimoyama M: Glutamic acid 207 in rodent T-cell RT6 antigens is essential for arginine-specific ADP-ribosylation. J Biol Chem 271: 29552–29555, 1996PubMedCrossRefGoogle Scholar
  68. 68.
    Okazaki IJ, Moss J: Mono-ADP-ribosylation: A reversible post-translational modification of proteins. Adv Pharmacol 35: 247–280, 1996PubMedCrossRefGoogle Scholar
  69. 69.
    Takada T, Iida K, Moss J: Conservation of a common motif in enzymes catalyzing ADP-ribose transfer. Identification of domains in mammalian transferases. J Biol Chem 270: 541–544, 1995PubMedCrossRefGoogle Scholar
  70. 70.
    Racke MK, Bonomo A, Scott DE, Cannella B, Levine A, Raine CS, Shevach EM, Röcken M: Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J Exp Med 180: 1961–1966, 1994PubMedCrossRefGoogle Scholar
  71. 71.
    Wang J, Nemoto E, Kots AY, Kaslow RK, Dennert G: Regulation of cytotoxic T cells by ecto-nicotinamide adenine dinucleotide (NAD) correlates with cell surface GPI-anchored/arginine ADP-ribosyl-transferase. J Immunol 153: 4048–4058, 1994PubMedGoogle Scholar
  72. 72.
    Nemoto E, Yu YJ, Dennert G: Cell surface ADP-ribosyltransferase regulates lymphocyte function-associated molecule-1 (LFA-1) function in T cells. J Immunol 157: 3341–3349, 1996PubMedGoogle Scholar
  73. 73.
    Nemoto E, Stohlman S, Dennert G: Release of a glycosylphos-phatidylinositol-anchored ADP-ribosyltransferase from cytotoxic T cells upon activation. J Immunol 156: 85–92, 1996PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Rita Bortell
    • 1
  • Toshihiro Kanaitsuka
    • 1
  • Linda A. Stevens
    • 2
  • Joel Moss
    • 2
  • John P. Mordes
    • 1
  • Aldo A. Rossini
    • 1
  • Dale L. Greiner
    • 1
    • 3
  1. 1.Department of MedicineUniversity of Massachusetts Medical CenterWorcesterUSA
  2. 2.Pulmonary-Critical Care Medicine BranchNational Heart, Lung, and Blood Institute, NIHBethesdaUSA
  3. 3.WorcesterUSA

Personalised recommendations