Invariant Chain Complexes and Clusters as Platforms for MIF Signaling
Invariant chain (Ii/CD74) has been identified as a surface receptor for migration inhibitory factor (MIF). Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II) molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric comp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-02-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/6/1/6 |
| _version_ | 1827841941365063680 |
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| author | Robert Lindner |
| author_facet | Robert Lindner |
| author_sort | Robert Lindner |
| collection | DOAJ |
| description | Invariant chain (Ii/CD74) has been identified as a surface receptor for migration inhibitory factor (MIF). Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II) molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric complexes consisting of one Ii trimer and three MHC II molecules (each of which is a heterodimer) has been regarded as a prerequisite for efficient delivery to the cell surface. Due to rapid endocytosis, however, only low levels of Ii-MHC II complexes are displayed on the cell surface of professional antigen presenting cells and very little free Ii trimers. The association of Ii and MHC II has been reported to block the interaction with MIF, thus questioning the role of surface Ii as a receptor for MIF on MHC II-expressing cells. Recent work offers a potential solution to this conundrum: Many Ii-complexes at the cell surface appear to be under-saturated with MHC II, leaving unoccupied Ii subunits as potential binding sites for MIF. Some of this work also sheds light on novel aspects of signal transduction by Ii-bound MIF in B-lymphocytes: membrane raft association of Ii-MHC II complexes enables MIF to target Ii-MHC II to antigen-clustered B-cell-receptors (BCR) and to foster BCR-driven signaling and intracellular trafficking. |
| first_indexed | 2024-03-12T08:00:54Z |
| format | Article |
| id | doaj.art-6bd633742cc84d7d883f5127b94c82a3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T08:00:54Z |
| publishDate | 2017-02-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-6bd633742cc84d7d883f5127b94c82a32023-09-02T19:51:52ZengMDPI AGCells2073-44092017-02-0161610.3390/cells6010006cells6010006Invariant Chain Complexes and Clusters as Platforms for MIF SignalingRobert Lindner0Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30625 Hannover, GermanyInvariant chain (Ii/CD74) has been identified as a surface receptor for migration inhibitory factor (MIF). Most cells that express Ii also synthesize major histocompatibility complex class II (MHC II) molecules, which depend on Ii as a chaperone and a targeting factor. The assembly of nonameric complexes consisting of one Ii trimer and three MHC II molecules (each of which is a heterodimer) has been regarded as a prerequisite for efficient delivery to the cell surface. Due to rapid endocytosis, however, only low levels of Ii-MHC II complexes are displayed on the cell surface of professional antigen presenting cells and very little free Ii trimers. The association of Ii and MHC II has been reported to block the interaction with MIF, thus questioning the role of surface Ii as a receptor for MIF on MHC II-expressing cells. Recent work offers a potential solution to this conundrum: Many Ii-complexes at the cell surface appear to be under-saturated with MHC II, leaving unoccupied Ii subunits as potential binding sites for MIF. Some of this work also sheds light on novel aspects of signal transduction by Ii-bound MIF in B-lymphocytes: membrane raft association of Ii-MHC II complexes enables MIF to target Ii-MHC II to antigen-clustered B-cell-receptors (BCR) and to foster BCR-driven signaling and intracellular trafficking.http://www.mdpi.com/2073-4409/6/1/6invariant chainIiCD74MHC IIB-cell receptorBCRantigen presentationmigration inhibitory factorMIFCD44membrane raft |
| spellingShingle | Robert Lindner Invariant Chain Complexes and Clusters as Platforms for MIF Signaling Cells invariant chain Ii CD74 MHC II B-cell receptor BCR antigen presentation migration inhibitory factor MIF CD44 membrane raft |
| title | Invariant Chain Complexes and Clusters as Platforms for MIF Signaling |
| title_full | Invariant Chain Complexes and Clusters as Platforms for MIF Signaling |
| title_fullStr | Invariant Chain Complexes and Clusters as Platforms for MIF Signaling |
| title_full_unstemmed | Invariant Chain Complexes and Clusters as Platforms for MIF Signaling |
| title_short | Invariant Chain Complexes and Clusters as Platforms for MIF Signaling |
| title_sort | invariant chain complexes and clusters as platforms for mif signaling |
| topic | invariant chain Ii CD74 MHC II B-cell receptor BCR antigen presentation migration inhibitory factor MIF CD44 membrane raft |
| url | http://www.mdpi.com/2073-4409/6/1/6 |
| work_keys_str_mv | AT robertlindner invariantchaincomplexesandclustersasplatformsformifsignaling |