Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)
Dale Christiansen
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorEffie Mouhtouris
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorJulie Milland
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorAlessandra Zingoni
Department of Experimental Medicine and Pathology, Instituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy
Search for more papers by this authorAngela Santoni
Department of Experimental Medicine and Pathology, Instituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy
Search for more papers by this authorMauro S. Sandrin
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorDale Christiansen
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorEffie Mouhtouris
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorJulie Milland
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorAlessandra Zingoni
Department of Experimental Medicine and Pathology, Instituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy
Search for more papers by this authorAngela Santoni
Department of Experimental Medicine and Pathology, Instituto Pasteur-Fondazione Cenci Bolognetti, University La Sapienza, Rome, Italy
Search for more papers by this authorMauro S. Sandrin
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia
Search for more papers by this authorAbstract
Abstract: Background: Many immunologically important interactions are mediated by leukocyte recognition of carbohydrates via cell surface receptors. Uncharacterized receptors on human natural killer (NK) cells interact with ligands containing the terminal Galα(1,3)Gal xenoepitope. The aim of this work was to isolate and characterize carbohydrate binding proteins from NK cells that bind αGal or other potential xenoepitopes, such as N-acetyllactosamine (NAcLac), created by the deletion of α1,3galactosyltransferase (GT) in animals.
Methods and results: Initial analysis suggested the human C-type lectin NKRP1A bound to a pool of glycoconjugates, the majority of which contained the terminal Galα(1,3)Gal epitope. This was confirmed by high level binding of cells expressing NKRP1A to mouse laminin, which contains a large number of N-linked oligosaccharides with the Galα(1,3)Gal structure. The consequence of removing the terminal αGal was then investigated. Elevated NAcLac levels were observed on thymocytes from GT−/− mice. Exposing NAcLac on laminin, by α-galactosidase treatment, resulted in a significant increase in NKRP1A binding.
Conclusions: NKRPIA binds to the αGal epitope. Moreover, exposing NAcLac by removal of αGal resulted in an increase in binding. This may be relevant in the later phases of xenotransplant rejection if GT−/− pigs, like GT−/− mice, display increased NAcLac expression.
References
- 1 Sandrin MS, McKenzie IF. Gal alpha (1,3)Gal, the major xenoantigen(s) recognised in pigs by human natural antibodies. Immunol Rev 1994; 141: 169.
- 2 Sandrin MS, Vaughan HA, Dabkowski PL et al. Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1–3)Gal epitopes. Proc Natl Acad Sci U S A 1993; 90: 11391.
- 3 Bach FH, Winkler H, Ferran C et al. Delayed xenograft rejection. Immunol Today 1996; 17: 379.
- 4 Sandrin MS, McKenzie IF. Recent advances in xenotransplantation. Curr Opin Immunol 1999; 11: 527.
- 5 Lin SS, Hanaway MJ, Gonzalez-Stawinski GV et al. The role of anti-Galalpha-3Gal antibodies in acute vascular rejection and accommodation of xenografts. Transplantation 2000; 70: 1667.
- 6 Dawson JR, Vidal AC, Malyguine AM. Natural killer cell-endothelial cell interactions in xenotransplantation. Immunol Res 2000; 22: 165.
- 7 Artrip JH, Kwiatkowski P, Michler RE et al. Target cell susceptibility to lysis by human natural killer cells is augmented by alpha(1,3)-galactosyltransferase and reduced by alpha(1,2)-fucosyltransferase. J Biol Chem 1999; 274: 10717.
- 8 Costa C, Barber DF, Fodor WL. Human NK cell-mediated cytotoxicity triggered by CD86 and Gal alpha 1,3-Gal is inhibited in genetically modified porcine cells. J Immunol 2002; 168: 3808.
- 9 Inverardi L, Clissi B, Stolzer AL et al. Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 1997; 63: 1318.
- 10 Miyagawa S, Nakai R, Yamada M et al. Regulation of natural killer cell-mediated swine endothelial cell lysis through genetic remodeling of a glycoantigen. J Biochem (Tokyo) 1999; 126: 1067.
- 11 Baumann BC, Forte P, Hawley RJ et al. Lack of galactose-alpha-1,3-galactose expression on porcine endothelial cells prevents complement-induced lysis but not direct xenogeneic NK cytotoxicity. J Immunol 2004; 172: 6460.
- 12 Baumann BC, Schneider MK, Lilienfeld BG et al. Endothelial cells derived from pigs lacking Gal alpha(1,3)Gal: no reduction of human leukocyte adhesion and natural killer cell cytotoxicity. Transplantation 2005; 79: 1067.
- 13 He Z, Ehrnfelt C, Kumagai-Braesch M et al. Aberrant expression of alpha-Gal on primary human endothelium does not confer susceptibility to NK cell cytotoxicity or increased NK cell adhesion. Eur J Immunol 2004; 34: 1185.
- 14 Sheikh S, Parhar R, Kwaasi A et al. Alpha-Gal-independent dual recognition and activation of xenogeneic endothelial cells and human naive natural killer cells. Transplantation 2000; 70: 917.
- 15 Bezouska K, Vlahas G, Horvath O et al. Rat natural killer cell antigen, NKR-P1, related to C-type animal lectins is a carbohydrate-binding protein. J Biol Chem 1994; 269: 16945.
- 16
Kogelberg H,
Frenkiel TA,
Birdsall B
et al.
Binding of sucrose octasulphate to the C-type lectin-like domain of the recombinant natural killer cell receptor NKR-P1A observed by NMR spectroscopy.
Chembiochem
2002; 3: 1072.
10.1002/1439-7633(20021104)3:11<1072::AID-CBIC1072>3.0.CO;2-1 CAS PubMed Web of Science® Google Scholar
- 17 Pospisil M, Vannucci L, Horvath O et al. Cancer immunomodulation by carbohydrate ligands for the lymphocyte receptor NKR-P1. Int J Oncol 2000; 16: 267.
- 18 Semenuk T, Krist P, Pavlicek J et al. Synthesis of chitooligomer-based glycoconjugates and their binding to the rat natural killer cell activation receptor NKR-P1. Glycoconj J 2001; 18: 817.
- 19 Bezouska K, Kren V, Kieburg C et al. GlcNAc-terminated glycodendrimers form defined precipitates with the soluble dimeric receptor of rat natural killer cells, sNKR-P1A. FEBS Lett 1998; 426: 243.
- 20 Evans MJ, Hartman SL, Wolff DW et al. Rapid expression of an anti-human C5 chimeric Fab utilizing a vector that replicates in COS and 293 cells. J Immunol Methods 1995; 184: 123.
- 21 Seed B, Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A 1987; 84: 3365.
- 22 Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol 1967; 26: 365.
- 23 Vaughan HA, Oldenburg KR, Gallop MA et al. Recognition of an octapeptide sequence by multiple Gal-alpha(1,3)Gal-binding proteins. Xenotransplantation 1996; 3: 18.
- 24 Lanier LL. NK cell recognition. Annu Rev Immunol 2005; 23: 225.
- 25 Lazetic S, Chang C, Houchins JP et al. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol 1996; 157: 4741.
- 26 Chang C, Rodriguez A, Carretero M et al. Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol 1995; 25: 2433.
- 27 Lai L, Kolber-Simonds D, Park KW et al. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 2002; 295: 1089.
- 28 Phelps CJ, Koike C, Vaught TD et al. Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 2003; 299: 411.
- 29 Sharma A, Naziruddin B, Cui C et al. Pig cells that lack the gene for alpha1–3 galactosyltransferase express low levels of the Gal antigen. Transplantation 2003; 75: 430.
- 30 Keusch JJ, Manzella SM, Nyame KA et al. Expression cloning of a new member of the ABO blood group glycosyltransferases, iGb3 synthase, that directs the synthesis of isoglobo-glycosphingolipids. J Biol Chem 2000; 275: 25308.
- 31 Milland J, Christiansen D, Lazarus BD et al. The molecular basis for Galalpha(1,3)Gal expression in animals with a deletion of the alpha1,3galactosyltransferase gene. J Immunol 2006; 176: 2448.
- 32 Zhou D, Mattner J, Cantu C 3rd et al. Lysosomal glycosphingolipid recognition by NKT cells. Science 2004; 306: 1786.
- 33 Watier H, Guillaumin JM, Piller F et al. Removal of terminal alpha-galactosyl residues from xenogeneic porcine endothelial cells. Decrease in complement-mediated cytotoxicity but persistence of IgG1-mediated antibody-dependent cell-mediated cytotoxicity. Transplantation 1996; 62: 105.
- 34 Shinkel TA, Chen CG, Salvaris E et al. Changes in cell surface glycosylation in alpha1,3-galactosyltransferase knockout and alpha1,2-fucosyltransferase transgenic mice. Transplantation 1997; 64: 197.
- 35 Aldemir H, Prod'homme V, Dumaurier MJ et al. Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor. J Immunol 2005; 175: 7791.
- 36 Rosen DB, Bettadapura J, Alsharifi M et al. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol 2005; 175: 7796.
- 37 Lanier LL, Chang C, Phillips JH. Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol 1994; 153: 2417.
- 38 Ryan JC, Niemi EC, Nakamura MC et al. NKR-P1A is a target-specific receptor that activates natural killer cell cytotoxicity. J Exp Med 1995; 181: 1911.
- 39
Poggi A,
Costa P,
Tomasello E
et al.
IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent NKRP1A-mediated down-regulation of NK cell activation.
Eur J Immunol
1998; 28: 1611.
10.1002/(SICI)1521-4141(199805)28:05<1611::AID-IMMU1611>3.0.CO;2-6 CAS PubMed Web of Science® Google Scholar
- 40 Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 1995; 13: 251.
- 41 Poggi A, Rubartelli A, Moretta L et al. Expression and function of NKRP1A molecule on human monocytes and dendritic cells. Eur J Immunol 1997; 27: 2965.
- 42 Goodman DJ, Von Albertini M, Willson A et al. Direct activation of porcine endothelial cells by human natural killer cells. Transplantation 1996; 61: 763.
- 43 Itescu S, Kwiatkowski P, Artrip JH et al. Role of natural killer cells, macrophages, and accessory molecule interactions in the rejection of pig-to-primate xenografts beyond the hyperacute period. Hum Immunol 1998; 59: 275.
- 44 Simons K, Ikonen E. Functional rafts in cell membranes. Nature 1997; 387: 569.
