Structural Basis for Lipid-Antigen Recognition in Avian Immunity1,2

• Published in: The Journal of immunology (1950) Vol. 184; no. 5; pp. 2504 - 2511
• Main Authors: Dvir, Hay, Wang, Jing, Ly, Nary, Dascher, Christopher C., Zajonc, Dirk M.
• Format: Journal Article
• Language: English
• Published: 25.01.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903509

CD1 proteins present self and foreign lipid antigens to activate specific T cells in the mammalian immune system. These T cells play an important role in controlling autoimmune diseases, suppression of tumor growth and host defense against invading pathogens. Humans utilize five CD1 isoforms, while only two exist in birds. Unlike mammals CD1, the structure of chicken CD1-2, showed a primitive lipid-binding groove, suggesting that chicken may only recognize single chain lipids. In contrast, the crystal structure of the second chicken CD1 isoform, chCD1-1, reported here at 2.2 Å resolution, reveals an elaborated binding groove with a dual-pocket dual-cleft architecture. The A′ and F′ deep pockets are separated from each other, but each is connected to a hydrophobic surface cleft, which may participate in lipids binding. The long endogenous ligand found inside the binding groove of chCD1-1, together with binding data on various glycolipids and mycolic acid, strongly suggest that the unique avian CD1 family could bind long dual- and possibly tri-acyl chain lipids.