Interaction of invariant chain trimer and MHC II alpha beta dimer

Stable Identifier
R-HSA-2130478
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
8148318 Class II histocompatibility molecules associate with calnexin during assembly in the endoplasmic reticulum

Schreiber, KL, Bell, MP, Huntoon, CJ, Rajagopalan, S, Brenner, MB, McKean, DJ

Int Immunol 1994
8313912 A role for calnexin (IP90) in the assembly of class II MHC molecules

Anderson, KS, Cresswell, P

EMBO J 1994
2190094 Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding

Roche, PA, Cresswell, P

Nature 1990
21116285 Invariant chain increases the half-life of MHC II by delaying endosomal maturation

Landsverk, OJ, Barois, N, Gregers, TF, Bakke, O

Immunol Cell Biol 2011
9312039 Interaction of MHC class II molecules with the invariant chain: role of the invariant chain (81-90) region

Stumptner, P, Benaroch, P

EMBO J 1997
1956401 Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain

Roche, PA, Marks, MS, Cresswell, P

Nature 1991
16618111 Invariant chain transmembrane domain trimerization: a step in MHC class II assembly

Dixon, AM, Stanley, BJ, Matthews, EE, Dawson, JP, Engelman, DM

Biochemistry 2006
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