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Cells 2017, 6(1), 6; doi:10.3390/cells6010006

Invariant Chain Complexes and Clusters as Platforms for MIF Signaling

Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30625 Hannover, Germany
Academic Editor: Ritva Tikkanen
Received: 8 December 2016 / Revised: 5 February 2017 / Accepted: 7 February 2017 / Published: 10 February 2017
(This article belongs to the Special Issue Signal Transduction 2016)
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Abstract

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. View Full-Text
Keywords: invariant chain; Ii; CD74; MHC II; B-cell receptor; BCR; antigen presentation; migration inhibitory factor; MIF; CD44; membrane raft invariant chain; Ii; CD74; MHC II; B-cell receptor; BCR; antigen presentation; migration inhibitory factor; MIF; CD44; membrane raft
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lindner, R. Invariant Chain Complexes and Clusters as Platforms for MIF Signaling. Cells 2017, 6, 6.

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