Gautam A M, Pearson C, Quinn V, McDevitt H O, Milburn P J
Department of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):335-9. doi: 10.1073/pnas.92.1.335.
Invariant chain (Ii) associates with major histocompatibility complex (MHC) class II molecules and is crucial for antigen presentation by class II molecules. The exact nature of Ii interaction with MHC class II molecules remains undefined. A nested set of Ii peptides, CLIPs (class II-associated Ii peptides), have been eluted from various MHC class II molecules, suggesting that CLIPs correspond, at least in part, to the Ii motif which blocks the conventional peptide binding site in MHC class II molecules. Here we report how CLIPs interact with class II MHC molecules, I-A. We have identified regions critical for binding of CLIPs and I-A class II molecules. In most cases, the binding of CLIPs to a number of I-A molecules is modulated by the steric bulk of methionine residues at positions 93 and 99. In addition, the binding of CLIPs to an I-A molecule, I-Au, is sensitive to substitutions at aspartic acid-59 in the alpha chain and threonine-86 in the beta chain, whereas the binding of an antigen-derived peptide is not. Taken together, these results provide an insight as to how CLIPs bind to MHC class II heterodimers.
恒定链（Ii）与主要组织相容性复合体（MHC）II类分子结合，对于II类分子的抗原呈递至关重要。Ii与MHC II类分子相互作用的确切性质仍不明确。一组嵌套的Ii肽，即CLIPs（II类相关Ii肽），已从各种MHC II类分子中洗脱出来，这表明CLIPs至少部分对应于Ii基序，该基序可阻断MHC II类分子中的常规肽结合位点。在此我们报告CLIPs如何与II类MHC分子I-A相互作用。我们已确定了对于CLIPs与I-A II类分子结合至关重要的区域。在大多数情况下，CLIPs与多种I-A分子的结合受93位和99位甲硫氨酸残基空间位阻的调节。此外，CLIPs与I-A分子I-Au的结合对α链中59位天冬氨酸和β链中86位苏氨酸的取代敏感，而抗原衍生肽的结合则不敏感。综上所述，这些结果为CLIPs如何结合MHC II类异二聚体提供了见解。
