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 Gal α (1,3)Gal xenoepitope. The aim of this work was to isolate and characterize carbohydrate binding proteins from NK cells that bind α Gal or other potential xenoepitopes, such as N ‐acetyllactosamine (NAcLac), created by the deletion of α 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 α (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 α (1,3)Gal structure. The consequence of removing the terminal α Gal 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 α Gal epitope. Moreover, exposing NAcLac by removal of α 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.