Lung dendritic cells are primed by inhaled particulate antigens, and retain MHC class II/antigenic peptide complexes in hilar lymph nodes for a prolonged period of time

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II–peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II–peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor α, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II–HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC–peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II–peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II–peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.

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T84-Intestinal Epithelial Exosomes Bear MHC Class II/Peptide Complexes Potentiating Antigen Presentation by Dendritic Cells

Gastroenterology ◽

10.1053/j.gastro.2007.02.043 ◽

2007 ◽

Vol 132 (5) ◽

pp. 1866-1876 ◽

Cited By ~ 139

Author(s):

Julia Mallegol ◽

Guillaume Van Niel ◽

Corinne Lebreton ◽

Yves Lepelletier ◽

Céline Candalh ◽

...

Keyword(s):

Dendritic Cells ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Class Ii ◽

Intestinal Epithelial ◽

Peptide Complexes

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Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b+ dendritic cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1513532112 ◽

2015 ◽

Vol 112 (41) ◽

pp. 12782-12787 ◽

Cited By ~ 30

Author(s):

Jonathan L. Linehan ◽

Thamotharampillai Dileepan ◽

Sakeen W. Kashem ◽

Daniel H. Kaplan ◽

Patrick Cleary ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Lymph Nodes ◽

Mhc Class Ii ◽

Th17 Cells ◽

Cell Subset ◽

Class Ii ◽

Dendritic Cell Subset ◽

Cervical Lymph Nodes ◽

Tgf Β1

Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the basis for this anatomic preference by tracking polyclonal CD4+ T cells specific for an MHC class II-bound peptide from the mucosal pathogen Streptococcus pyogenes. S. pyogenes MHC class II-bound peptide-specific CD4+ T cells were first activated in the cervical lymph nodes following i.n. inoculation and then differentiated into Th17 cells. S. pyogenes-induced Th17 formation depended on TGF-β1 from dendritic cells and IL-6 from a CD301b+ dendritic cell subset located in the cervical lymph nodes but not the spleen. Thus, the tendency of i.n. infection to induce Th17 cells is related to cytokine production by specialized dendritic cells that drain this site.

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Dendritic cells constitutively present self antigens in their immature state in vivo and regulate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis

Blood ◽

10.1182/blood-2003-08-2729 ◽

2004 ◽

Vol 103 (6) ◽

pp. 2187-2195 ◽

Cited By ~ 123

Author(s):

Nicholas S. Wilson ◽

Dima El-Sukkari ◽

José A. Villadangos

Keyword(s):

Dendritic Cells ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Class Ii ◽

Lymphoid Organ ◽

Lymphoid Organs ◽

Mhc Ii ◽

Peptide Complexes ◽

Self Antigens

Abstract Dendritic cells (DCs) change their antigen-presenting properties during maturation. Immature DCs efficiently capture antigens, but are reported to be impaired in their processing and presenting capacity. Upon an encounter with an inflammatory stimulus, DCs undergo a maturation process that leads to efficient presentation of antigens captured at the time of activation, but precludes processing of antigens encountered at later time points. The mechanisms that underlie these developmental changes are controversial. Thus, it is unclear whether immature DCs can present self antigens, and which are the checkpoints that regulate antigen presentation in immature and mature DCs. We have characterized these mechanisms using DCs derived directly from lymphoid organs. Immature lymphoid organ DCs constitutively presented self peptides bound to major histocompatibility complex class II (MHCII) molecules, but these MHCII-peptide complexes were degraded quickly after their transient expression on the cell surface. During maturation, MHC II endocytosis was down-regulated, so that newly generated MHC II–peptide complexes accumulated on the plasma membrane. Simultaneously, MHC II synthesis was down-regulated, thus preventing the turnover of the MHC II–peptide complexes that accumulated early during maturation. Our results demonstrate that immature DCs constitutively present self antigens in the lymphoid organs and characterize the molecular basis of the capacity of DCs to provide “antigenic memory” in vivo.

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Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II–positive Dendritic Cells Derived from MHC Class II–negative Grafts

Journal of Experimental Medicine ◽

10.1084/jem.20010838 ◽

2002 ◽

Vol 195 (2) ◽

pp. 259-268 ◽

Cited By ~ 133

Author(s):

Ying Liu ◽

Pedram Hamrah ◽

Qiang Zhang ◽

Andrew W. Taylor ◽

M. Reza Dana

Keyword(s):

Dendritic Cells ◽

Major Histocompatibility Complex ◽

Lymph Nodes ◽

Mhc Class Ii ◽

Fluorescent Protein ◽

Class Ii ◽

Corneal Transplant ◽

Dependent Manner ◽

Major Histocompatibility ◽

Histocompatibility Complex

To examine the widely accepted dogmas that corneal grafts lack passenger leukocytes or cells capable of migrating directly to lymph nodes (LNs), we tracked the migration of corneal graft-derived transgenic green fluorescent protein (GFP; Iab) cells into the draining LNs of allogeneic (Iad) recipients. GFP+ cells were identified in cervical LNs several hours after transplantation, and this traffic was significantly enhanced when grafts were placed in inflamed recipient beds. Draining cells were Iab+, CD45+, and CD11c+, and examination of ungrafted corneas revealed numerous similarly CD45+CD11c+CD3−CD8α− cells that uniformly lacked major histocompatibility complex (MHC) class II expression; transmission electron microscopy confirmed the presence of morphologically similar cells. After transplantation, or placement in culture, these CD11c+ cells became class II+ in a time-dependent manner and were capable of allostimulatory function. However, the stimulatory capacity of these cornea-derived dendritic cells (DCs) was suppressed compared with splenic controls. These results demonstrate for the first time that the cornea is endowed with resident DCs that are universally MHC class II− but that are capable of expressing class II antigen after surgery and migrating to draining LNs of allografted hosts. These data refute the tenet that the cornea is immune privileged due to lack of resident lymphoreticular cells or due to antigenic sequestration from systemic immunity.

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