Interaction of invariant chain trimer and MHC II alpha beta dimer

MHC II alpha beta dimers associate with a third polypeptide, the invariant chain (Ii), required for class II molecules to reach the endocytic pathway (Roche et al. 1991). The interaction of Ii with the MHC II alpha beta dimer serves multiple functions. It plays a role in assembly, folding, egress from the ER and transport through the Golgi. Ii exists as a trimer; residues 163-183 of the Ii lumenal domain are involved in covalent cross-linking. Residues 96-104 are critical for association with class II alpha beta dimers (Bijlmakers et al. 1994, Freisewinkel et al. 1993). Residues 89-104 known as CLIP (Class II-associated invariant chain peptide) are the part of the Ii chain that binds antigen binding MHC class II groove, remaining bound until the MHC receptor is completely assembled. This CLIP domain prevents the premature binding of self-peptide fragments present in ER prior to MHC II localization within the endosomal compartment. The ER-resident chaperone protein calnexin rapidly associates with newly synthesized alpha, beta and invariant chains, and remains associated until the final nonamer assembly. The stoichiometry of calnexin in this interaction and the dynamics of association-dissociation are not known. Calnexin may stabilize the free class II chains and regulate their intracellular transport by facilitating the production of transport competent molecules out of the ER (Anderson & Cresswell 1994, Schreiber et al. 1995).

MHC II αβ二聚体与第三种多肽，即不变链（Ii），相结合，该链对于II类分子进入内吞途径（Roche 等人，1991年）至关重要。Ii与MHC II αβ二聚体的相互作用发挥着多重功能。它在组装、折叠、从内质网中释放以及通过高尔基体的运输过程中扮演着关键角色。Ii以三聚体的形式存在；Ii腔内域的163-183位残基参与共价交联。96-104位残基对于与II类αβ二聚体的结合至关重要（Bijlmakers 等人，1994年，Freisewinkel 等人，1993年）。被称为CLIP（II类相关不变链肽）的89-104位残基是Ii链中与抗原结合的MHC II沟槽结合的部分，并保持结合状态，直到MHC受体的完全组装。此CLIP域阻止了存在于内质网中、在MHC II定位到内吞体腔室之前存在的自身肽片段的过早结合。内质网驻留的伴侣蛋白calnexin迅速与新合成的α、β和不变链结合，并保持结合状态，直至最终九聚体的组装。此相互作用中calnexin的化学计量比及其结合-解离的动力学尚不清楚。Calnexin可能通过促进具有运输能力的分子从内质网中产生，来稳定游离的II类链并调节其细胞内运输（Anderson 与 Cresswell，1994年，Schreiber 等人，1995年）。