Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)

Dale Christiansen, Effie Mouhtouris, Julie Milland, Alessandra Zingoni, Angela Santoni, Mauro S. Sandrin

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalXenotransplantation
Volume13
Issue number5
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Carbohydrates
Laminin
Natural Killer Cells
Epitopes
Galactosidases
C-Type Lectins
Glycoconjugates
Cell Surface Receptors
Thymocytes
Oligosaccharides
Leukocytes
Swine
N-acetyllactosamine
Ligands
galactosyl-(1-3)galactose

Keywords

  • α1,3galactosyltransferase knockout
  • Galα(1,3)Gal
  • N-acetyllactosamine
  • NKRP1A
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology

Cite this

Christiansen, D., Mouhtouris, E., Milland, J., Zingoni, A., Santoni, A., & Sandrin, M. S. (2006). Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161). Xenotransplantation, 13(5), 440-446. https://doi.org/10.1111/j.1399-3089.2006.00332.x

Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161). / Christiansen, Dale; Mouhtouris, Effie; Milland, Julie; Zingoni, Alessandra; Santoni, Angela; Sandrin, Mauro S.

In: Xenotransplantation, Vol. 13, No. 5, 09.2006, p. 440-446.

Research output: Contribution to journalArticle

Christiansen, D, Mouhtouris, E, Milland, J, Zingoni, A, Santoni, A & Sandrin, MS 2006, 'Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)', Xenotransplantation, vol. 13, no. 5, pp. 440-446. https://doi.org/10.1111/j.1399-3089.2006.00332.x
Christiansen D, Mouhtouris E, Milland J, Zingoni A, Santoni A, Sandrin MS. Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161). Xenotransplantation. 2006 Sep;13(5):440-446. https://doi.org/10.1111/j.1399-3089.2006.00332.x
Christiansen, Dale ; Mouhtouris, Effie ; Milland, Julie ; Zingoni, Alessandra ; Santoni, Angela ; Sandrin, Mauro S. / Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161). In: Xenotransplantation. 2006 ; Vol. 13, No. 5. pp. 440-446.
@article{2691bb60da2d4fafa97d5898e86b34c3,
title = "Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)",
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.",
keywords = "α1,3galactosyltransferase knockout, Galα(1,3)Gal, N-acetyllactosamine, NKRP1A, Xenotransplantation",
author = "Dale Christiansen and Effie Mouhtouris and Julie Milland and Alessandra Zingoni and Angela Santoni and Sandrin, {Mauro S.}",
year = "2006",
month = "9",
doi = "10.1111/j.1399-3089.2006.00332.x",
language = "English",
volume = "13",
pages = "440--446",
journal = "Xenotransplantation",
issn = "0908-665X",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)

AU - Christiansen, Dale

AU - Mouhtouris, Effie

AU - Milland, Julie

AU - Zingoni, Alessandra

AU - Santoni, Angela

AU - Sandrin, Mauro S.

PY - 2006/9

Y1 - 2006/9

N2 - 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.

AB - 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.

KW - α1,3galactosyltransferase knockout

KW - Galα(1,3)Gal

KW - N-acetyllactosamine

KW - NKRP1A

KW - Xenotransplantation

UR - http://www.scopus.com/inward/record.url?scp=33747627375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747627375&partnerID=8YFLogxK

U2 - 10.1111/j.1399-3089.2006.00332.x

DO - 10.1111/j.1399-3089.2006.00332.x

M3 - Article

C2 - 16925668

AN - SCOPUS:33747627375

VL - 13

SP - 440

EP - 446

JO - Xenotransplantation

JF - Xenotransplantation

SN - 0908-665X

IS - 5

ER -