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Recognition of a carbohydrate xenoepitope by human NKRP1A (CD161)
Author(s) -
Christiansen Dale,
Mouhtouris Effie,
Milland Julie,
Zingoni Alessandra,
Santoni Angela,
Sandrin Mauro S.
Publication year - 2006
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2006.00332.x
Subject(s) - glycoconjugate , epitope , receptor , lectin , laminin , microbiology and biotechnology , glycoprotein , chemistry , biology , cell , biochemistry , antigen , immunology
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.