Girardi Enrico, Wang Jing, Zajonc Dirk M
From the Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037 and.
From the Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037 and the Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
J Biol Chem. 2016 May 13;291(20):10677-83. doi: 10.1074/jbc.M115.702118. Epub 2016 Mar 22.
Mouse CD1d is a nonclassical MHC molecule able to present lipids and glycolipids to a specialized subset of T cells known as natural killer T cells. The antigens presented by CD1d have been shown to cover a broad range of chemical structures and to follow precise rules determining the potency of the antigen in the context of T cell activation. Together with lipids, initial reports suggested that CD1d can also bind and present hydrophobic peptides with (F/W)XX(I/L/M)XXW. However, the exact location of peptide binding and the molecular basis for the required motif are currently unknown. Here we present the crystal structure of the first peptide identified to bind CD1d, p99, and show that it binds in the antigen-binding groove of CD1d in a manner compatible with its presentation to T cell receptors. Interestingly, the peptide adopts an α-helical conformation, which orients the motif residues toward its deep binding groove, therefore explaining the molecular requirements for peptide binding. Moreover, we demonstrate that a lipopeptide version of the same peptide is able to bind CD1d in a similar conformation, identifying another class of molecules binding this antigen-presenting molecule.
小鼠CD1d是一种非经典的MHC分子，能够将脂质和糖脂呈递给一类特殊的T细胞亚群，即自然杀伤T细胞。已证明CD1d呈递的抗原涵盖广泛的化学结构，并遵循在T细胞活化背景下决定抗原效力的精确规则。与脂质一起，最初的报告表明CD1d也可以结合并呈递具有(F/W)XX(I/L/M)XXW基序的疏水肽。然而，目前尚不清楚肽结合的确切位置以及所需基序的分子基础。在此，我们展示了首个被鉴定为可结合CD1d的肽p99的晶体结构，并表明它以与其呈递给T细胞受体相兼容的方式结合在CD1d的抗原结合槽中。有趣的是，该肽采用α螺旋构象，将基序残基朝向其深结合槽定向，从而解释了肽结合的分子要求。此外，我们证明相同肽的脂肽版本能够以类似构象结合CD1d，确定了另一类结合这种抗原呈递分子的分子。
