Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161).
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 Galalpha(1,3)Gal xenoepitope. The aim of this work was to isolate and characterize carbohydrate binding proteins from NK cells that bind alphaGal or other potential xenoepitopes, such as N-acetyllactosamine (NAcLac), created by the deletion of alpha1,3galactosyltransferase (GT) in animals.


RESULTS
Initial analysis suggested the human C-type lectin NKRP1A bound to a pool of glycoconjugates, the majority of which contained the terminal Galalpha(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 Galalpha(1,3)Gal structure. The consequence of removing the terminal alphaGal was then investigated. Elevated NAcLac levels were observed on thymocytes from GT-/- mice. Exposing NAcLac on laminin, by alpha-galactosidase treatment, resulted in a significant increase in NKRP1A binding.


CONCLUSIONS
NKRPIA binds to the alphaGal epitope. Moreover, exposing NAcLac by removal of alphaGal 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.
Christiansen
Dale
D
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia.
Mouhtouris
Effie
E
Milland
Julie
J
Zingoni
Alessandra
A
Santoni
Angela
A
Sandrin
Mauro S
MS
D000606:Amino Sugars / Q000096:biosynthesis / Q000276:immunology; D000818:Animals; D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004187:Disaccharides / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014183:Transplantation, Heterologous / Q000276:immunology*
D000606:Amino Sugars; D000954:Antigens, Surface; D004187:Disaccharides; D000939:Epitopes; C527203:KLRB1 protein, human; D007797:Laminin; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; C055075:galactosyl-(1-3)galactose; C000458:N-acetyllactosamine