The MHC class II-associated invariant chain: a molecule with multiple roles in MHC class II biosynthesis and antigen presentation to CD4+ T cells.
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.
Bertolino
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P
ENS-Lyon, Laboratoire de Biologie, UMR 49, France.
Rabourdin-Combe
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C
D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000502:physiology*; D006801:Humans; D051379:Mice
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain