Christal structures of bovine CD1d reveal altered aGalCer presentation and a restricted A' pocket unable to bind long-chain glycolipids
| Autor: | Joren Guillaume, Serge Van Calenbergh, Ildiko Van Rhijn, Nora Pauwels, Dirk M. Zajonc, Jing Wang |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular AUTOIMMUNITY Glycobiology lcsh:Medicine Plasma protein binding Crystallography X-Ray Lymphocyte Activation Biochemistry Major Histocompatibility Complex Mice 0302 clinical medicine Biomacromolecule-Ligand Interactions lcsh:Science SULFATIDE Antigen Presentation 0303 health sciences Immune System Proteins Multidisciplinary Molecular Structure NKT CELLS T-CELL-RECEPTOR biology T Cells hemic and immune systems Natural killer T cell Lipids Recombinant Proteins FAMILY CD1D lipids (amino acids peptides and proteins) Protein Binding Research Article Veterinary Medicine Protein Structure PROTEINS Immune Cells Molecular Sequence Data Immunology Antigen presentation Galactosylceramides chemical and pharmacologic phenomena Major histocompatibility complex Veterinary Immunology 03 medical and health sciences Antigen MHC class I ANTIGEN PRESENTATION Animals Humans Amino Acid Sequence Biology 030304 developmental biology Sphingolipids Binding Sites Sulfoglycosphingolipids Sequence Homology Amino Acid T-cell receptor lcsh:R RECOGNITION Proteins Biology and Life Sciences Major Histocompatibility Antigens Protein Structure Tertiary MODEL carbohydrates (lipids) biology.protein Natural Killer T-Cells Cattle T-Cell Receptors Veterinary Science lcsh:Q Antigens CD1d Glycolipids 030215 immunology |
| Zdroj: | PLoS One, 7(10). Public Library of Science PLoS ONE, Vol 7, Iss 10, p e47989 (2012) PLOS ONE PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0047989 |
| Popis: | 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-alpha GalCer 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, alpha GalCer is presented differently at the cell surface, due to an amino acid Asp151Asn substitution that results in loss of intimate contacts between the alpha GalCer headgroup and CD1d. The altered alpha GalCer 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. |
| Databáze: | OpenAIRE |
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