4f7c

Publication Abstract from PubMed

NKT cells play important roles in immune surveillance. They rapidly respond to pathogens by detecting microbial glycolipids when presented by the non-classical MHC I homolog CD1d. Previously, ruminants were considered to lack NKT cells due to the lack of a functional CD1D gene. However, recent data suggest that cattle express CD1d with unknown function. In an attempt to characterize the function of bovine CD1d, we assessed the lipid binding properties of recombinant Bos taurus CD1d (boCD1d) in vitro. BoCD1d is able to bind glycosphingolipids (GSLs) with fatty acid chain lengths of C(18), while GSLs with fatty acids of C(24) do not bind. Crystal structures of boCD1d bound to a short-chain C(12)-di-sulfatide antigen, as well as short-chain C(16)-alphaGalCer revealed that the A pocket of boCD1d is restricted in size compared to that of both mouse and human CD1d, explaining the inability of long chain GSL's to bind to boCD1d. Moreover, while di-sulfatide is presented similarly compared to the presentation of sulfatide by mouse CD1d, alphaGalCer is presented differently at the cell surface, due to an amino acid Asp151Asn substitution that results in loss of intimate contacts between the alphaGalCer headgroup and CD1d. The altered alphaGalCer presentation by boCD1d also explains its lack of cross-activation of mouse iNKT cells and raises the interesting question of the nature and function of bovine lipid-reactive T cells.

Crystal Structures of Bovine CD1d Reveal Altered alphaGalCer Presentation and a Restricted A' Pocket Unable to Bind Long-Chain Glycolipids.,Wang J, Guillaume J, Pauwels N, Van Calenbergh S, Van Rhijn I, Zajonc DM PLoS One. 2012;7(10):e47989. doi: 10.1371/journal.pone.0047989. Epub 2012 Oct 23. PMID:23110152^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.