Department of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla CA 92037, USA.
J Immunol. 2010 Mar 1;184(5):2504-11. doi: 10.4049/jimmunol.0903509. Epub 2010 Jan 25.
CD1 proteins present self- and foreign lipid Ags 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 use five CD1 isoforms, whereas 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 in this study at 2.2 A 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 lipid 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 triacyl-chain lipids.
CD1 蛋白将自身和外源脂质抗原呈递给哺乳动物免疫系统中的特定 T 细胞。这些 T 细胞在控制自身免疫性疾病、抑制肿瘤生长和宿主抵御入侵病原体方面发挥着重要作用。人类使用五种 CD1 同种型，而鸟类仅存在两种。与哺乳动物的 CD1 不同，鸡 CD1-2 的结构显示出原始的脂质结合槽，表明鸡可能仅识别单链脂质。相比之下，本研究报道的第二个鸡 CD1 同种型 chCD1-1 的晶体结构分辨率为 2.2Å，揭示了一个精细的结合槽，具有双口袋、双裂隙结构。A'和 F'深口袋彼此分离，但每个口袋都与一个疏水性表面裂隙相连，该裂隙可能参与脂质结合。在 chCD1-1 的结合槽内发现的长内源性配体，以及对各种糖脂和分枝菌酸的结合数据，强烈表明独特的禽类 CD1 家族可以结合长的双和可能的三酰链脂质。
