Bertolino P, Rabourdin-Combe C
ENS-Lyon, Laboratoire de Biologie, UMR 49, France.
Crit Rev Immunol. 1996;16(4):359-79.
The MHC class II-associated invariant chain (Ii) plays a central role in the biological function of MHC class II molecules. Ii is a type II membrane glycoprotein that is synthesized as different isoforms that include a major 31 kDa isoform (p31/p33) and a minor 41 kDa isoform (p41) in both, mice and humans. All isoforms share several common regions acting at different steps in the process that lead to functional class II molecule/peptide complexes. In the ER, two C-terminal extracytoplasmic regions of Ii are required for class II assembly: the 153-183 region is involved in the formation of Ii trimers and the 80-104 region mediates binding with class II molecules giving rise to nonamers. Ii association with class II molecules prevents both aggregation of class II dimers and binding with endogenous ER-derived peptides. In addition, two motifs in the cytosolic N-terminal region of Ii direct class II nonamers toward specialized endosomal compartments where peptide loading occurs. In these compartments, Ii undergoes proteolytic degradation leaving only CLIP (residues 80-104) associated with Class II. CLIP modulates loading of class II molecules in endosomes and is removed from the MHC class II groove by monomorphic MHC class II molecules, H2-M or HLA DM, in mouse and human, respectively. The roles of Ii in antigen presentation to MHC class II-restricted T cells and in CD4+ T cell development are discussed in this review.
MHC II类分子相关恒定链（Ii）在MHC II类分子的生物学功能中起核心作用。Ii是一种II型膜糖蛋白，在小鼠和人类中均以不同的异构体形式合成，包括主要的31 kDa异构体（p31/p33）和次要的41 kDa异构体（p41）。所有异构体都共享几个共同区域，这些区域在导致功能性II类分子/肽复合物形成的过程中发挥不同作用。在内质网中，Ii的两个C末端胞外区域是II类组装所必需的：153-183区域参与Ii三聚体的形成，80-104区域介导与II类分子的结合，从而形成九聚体。Ii与II类分子的结合可防止II类二聚体的聚集以及与内源性内质网衍生肽的结合。此外，Ii胞质N末端区域的两个基序将II类九聚体导向发生肽加载的特殊内体区室。在这些区室中，Ii经历蛋白水解降解，仅留下与II类相关的CLIP（80-104位残基）。CLIP调节II类分子在内体中的加载，并分别被小鼠和人类中的单态性MHC II类分子H2-M或HLA DM从MHC II类凹槽中去除。本文综述了Ii在向MHC II类限制性T细胞呈递抗原以及CD4+ T细胞发育中的作用。
