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 Gal alpha(1,3)Gal xenoepitope. The aim of this work was to isolate and characterize carbohydrate binding proteins from NK cells that bind alpha Gal or other potential xenoepitopes, such as N-acetyllactosamine (NAcLac), created by the deletion of alpha 1,3galactosyltransferase (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 Gal alpha(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 Gal alpha(1,3)Gal structure. The consequence of removing the terminal alpha Gal 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 alpha Gal epitope. Moreover, exposing NAcLac by removal of alpha Gal 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.
Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161) / Dale, Christiansen; Effie, Mouhtouris; Julie, Milland; Zingoni, Alessandra; Santoni, Angela; Mauro S., Sandrin. - In: XENOTRANSPLANTATION. - ISSN 0908-665X. - STAMPA. - 13:5(2006), pp. 440-446. [10.1111/j.1399-3089.2006.00332.x]
Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)
ZINGONI, Alessandra;SANTONI, Angela;
2006
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 Gal alpha(1,3)Gal xenoepitope. The aim of this work was to isolate and characterize carbohydrate binding proteins from NK cells that bind alpha Gal or other potential xenoepitopes, such as N-acetyllactosamine (NAcLac), created by the deletion of alpha 1,3galactosyltransferase (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 Gal alpha(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 Gal alpha(1,3)Gal structure. The consequence of removing the terminal alpha Gal 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 alpha Gal epitope. Moreover, exposing NAcLac by removal of alpha Gal 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.