The multifaceted roles of the invariant chain CD74 — More than just a chaperone

Schröder, Bernd

doi:10.1016/j.bbamcr.2016.03.026

Cited by 191 publications

(217 citation statements)

References 142 publications

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“…Rather, this Ii domain initiates a signaling cascade, resulting in NFkB activation and B cell maintenance (152). The intramembrane protease SPPL2a (presenilin homolog signal-peptide-peptidase-like 2a) catalyzes the generation of this Ii fragment in mice and human B cells (153) Ii has third role for B cells as the receptor for macrophage migration inhibitory factor and interaction leads to signaling cascade that promotes B cell chemotaxis and survival (154). …”

Section: Mhcii Antigen Presentation Over the Span Of B Cell Developmentmentioning

confidence: 99%

The Other Function: Class II-Restricted Antigen Presentation by B Cells

et al. 2017

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Mature B lymphocytes (B cells) recognize antigens using their B cell receptor (BCR) and are activated to become antibody-producing cells. In addition, and integral to the development of a high-affinity antibodies, B cells utilize the specialized major histocompatibility complex class II (MHCII) antigen presentation pathway to process BCR-bound and internalized protein antigens and present selected peptides in complex with MHCII to CD4+ T cells. This interaction influences the fate of both types of lymphocytes and shapes immune outcomes. Specific, effective, and optimally timed antigen presentation by B cells requires well-controlled intracellular machinery, often regulated by the combined effects of several molecular events. Here, we delineate and summarize these events in four steps along the antigen presentation pathway: (1) antigen capture and uptake by B cells; (2) intersection of internalized antigen/BCRs complexes with MHCII in peptide-loading compartments; (3) generation and regulation of MHCII/peptide complexes; and (4) exocytic transport for presentation of MHCII/peptide complexes at the surface of B cells. Finally, we discuss modulation of the MHCII presentation pathway across B cell development and maturation to effector cells, with an emphasis on the shaping of the MHCII/peptide repertoire by two key antigen presentation regulators in B cells: HLA-DM and HLA-DO.

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Section: Mhcii Antigen Presentation Over the Span Of B Cell Developmentmentioning

confidence: 99%

The Other Function: Class II-Restricted Antigen Presentation by B Cells

et al. 2017

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“…It is cleared from the membrane by regulated intramembrane proteolysis (RIP), which causes the two resulting fragments to be released to either side of the membrane. This process resembles the way in which the intra-membrane proteases presenillin and signal peptidase act on their substrates [30]. The protease in charge of cleaving NTF within the membrane has recently been identified as a member of the signal peptidase family and has been termed signal peptide peptidase-like 2a (SPPL-2a) [98,99,100,101].…”

Section: Mif-induced Signaling From Invariant Chain Complexesmentioning

confidence: 99%

“…Here, I will provide a short overview of both lives of Ii and then briefly discuss new results that show promise to integrate the two fields. Invariant chain has been the topic of an excellent recent review by Schröder [30] and the readers are referred to this paper for a concise coverage of Ii biology.…”

Section: Introductionmentioning

confidence: 99%

Invariant Chain Complexes and Clusters as Platforms for MIF Signaling

Lindner

2017

Cells

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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.

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“…Moreover, load-independent changes were also evidenced on the non-CCL treated contralateral limb, indicating a systemic response of the massage-mimetic treatment [46]. From the 47% of the functional gene ontology clusters associating with immune response after CCL, the authors validated the chemokine (C-C motif) receptor CCR2, a critical regulator of skeletal muscle regeneration [47,48]; the leukocyte immunoglobulin like receptor B4 (Lilrb4), alias ILT3, thought to control inflammatory responses and limit autoreactivity through Treg enhancement [49]; the major histocompatibility complex (class II) molecule Cd74, an important regulator of immunity and inflammation with an impact on the cell endosomal compartment [50]; and the lysozyme 2 (Lyz2) gene involved in activities such as reducing the presence of proinflammatory cytokines (TNF-α, IL-6, INF-γ, IL-8 and IL-17) while increasing levels of anti-inflammatory cytokines (IL-4 and TGF-β) [51]; by the cost-effective alternative approach RT-qPCR (real time polymerase chain reaction after retrotranscription) which entitles a rather easy implementation of molecular marker monitorization in follow-up studies. All these molecular changes appeared unaffected in low load treatments (1.4 N) and upregulated by medium load treatments (4.5 N) indicating that a minimum pressure is required to register the effect.…”

Section: Neuroimmune Impact Of Mtmentioning

confidence: 99%

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

Espejo¹,

García-Escudero²,

Oltra³

2018

Preprint

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Abstract:Application of protocols without parameter standardization and rigorous controls has led manual therapy (MT) and other physiotherapy approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way this can be achieved is by studying gene expression and additional physiological changes that associate to particular, parameter-controlled, treatments in animal models and translating this knowledge to properly design objective, quantitatively-monitored clinical trials. Here, we propose a Molecular Physiotherapy Approach (MPTA), requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports of MT that historically attribute benefits to these treatments. The review focuses in the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and CFS/ME. The systemic effect associated to mechanical-load responses is considered of particular relevance as it suggests that defined, low-pain areas could be selected for treatments with overall benefits, an aspect that might result essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to treat FM and CFS/ME.

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The multifaceted roles of the invariant chain CD74 — More than just a chaperone

Cited by 191 publications

References 142 publications

The Other Function: Class II-Restricted Antigen Presentation by B Cells

The Other Function: Class II-Restricted Antigen Presentation by B Cells

Invariant Chain Complexes and Clusters as Platforms for MIF Signaling

Unraveling molecular determinants of manual therapy: an approach to integrative therapeutics for the treatment of fibromyalgia and CFS/ME

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