scholarly journals Disruption of Multivesicular Body Vesicles Does Not Affect Major Histocompatibility Complex (MHC) Class II-Peptide Complex Formation and Antigen Presentation by Dendritic Cells

2013 ◽  
Vol 288 (34) ◽  
pp. 24286-24292 ◽  
Author(s):  
Berta Bosch ◽  
Adam C. Berger ◽  
Sanjay Khandelwal ◽  
Erica L. Heipertz ◽  
Brian Scharf ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Complex Formation ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Multivesicular Body ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Peptide Complex ◽  
Histocompatibility Complex

scholarly journals CD1 and Major Histocompatibility Complex II Molecules Follow a Different Course during Dendritic Cell Maturation

2003 ◽  
Vol 14 (8) ◽  
pp. 3378-3388 ◽  
Author(s):  
Nicole N. van der Wel ◽  
Masahiko Sugita ◽  
Donna M. Fluitsma ◽  
Xaiochun Cao ◽  
Gerty Schreibelt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Herein, we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady-state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to lipopolysaccharide-induced maturation. However, the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus, the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separate peptide- and lipid antigen-presenting molecules during dendritic cell maturation.

The FcγRIa (CD64) Ligand Binding Chain Triggers Major Histocompatibility Complex Class II Antigen Presentation Independently of Its Associated FcR γ-Chain

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 808-817 ◽  
Author(s):  
Martine J. van Vugt ◽  
Monique J. Kleijmeer ◽  
Tibor Keler ◽  
Ingrid Zeelenberg ◽  
Marc A. van Dijk ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Ligand Binding ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Rabbit Igg ◽  
Class Ii Antigen

Abstract Within multi-subunit Ig receptors, the FcR γ-chain immunoreceptor tyrosine-based activation motif (ITAM) plays a crucial role in enabling antigen presentation. This process involves antigen-capture and targeting to specific degradation and major histocompatibility complex (MHC) class II loading compartments. Antigenic epitopes are then presented by MHC class II molecules to specific T cells. The high-affinity receptor for IgG, hFcγRIa, is exclusively expressed on myeloid lineage cells and depends on the FcR γ-chain for surface expression, efficient ligand binding, and most phagocytic effector functions. However, we show in this report, using the IIA1.6 cell model, that hFcγRIa can potentiate MHC class II antigen presentation, independently of a functional FcR γ-chain ITAM. Immunoelectron microscopic analyses documented hFcγRIa -chain/rabbit IgG-Ovalbumin complexes to be internalized and to migrate via sorting endosomes to MHC class II-containing late endosomes. Radical deletion of the hFcγRIa -chain cytoplasmic tail did not affect internalization of rabbit IgG-Ovalbumin complexes. Importantly, however, this resulted in diversion of receptor-ligand complexes to the recycling pathway and decreased antigen presentation. These results show the hFcγRIa cytoplasmic tail to contain autonomous targeting information for intracellular trafficking of receptor-antigen complexes, although deficient in canonical tyrosine- or dileucine-targeting motifs. This is the first documentation of autonomous targeting by a member of the multichain FcR family that may critically impact the immunoregulatory role proposed for hFcγRIa (CD64).

scholarly journals Antigen Presentation by Dendritic Cells after Immunization with DNA Encoding a Major Histocompatibility Complex Class II–restricted Viral Epitope

1997 ◽  
Vol 186 (9) ◽  
pp. 1481-1486 ◽  
Author(s):  
Sofia Casares ◽  
Kayo Inaba ◽  
Teodor-Doru Brumeanu ◽  
Ralph M. Steinman ◽  
Constantin A. Bona
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Antigen Presentation ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Dna Encoding ◽  
Histocompatibility Complex

Intramuscular and intracutaneous immunization with naked DNA can vaccinate animals to the encoded proteins, but the underlying mechanisms of antigen presentation are unclear. We used DNA that encodes an A/PR/8/34 influenza peptide for CD4 T cells and that elicits protective antiviral immunity. DNA-transfected, cultured muscle cells released the influenza polypeptide, which then could be presented on the major histocompatibility complex class II molecules of dendritic cells. When DNA was injected into muscles or skin, and antigen-presenting cells were isolated from either the draining lymph nodes or the skin, dendritic, but not B, cells presented antigen to T cells and carried plasmid DNA. We suggest that the uptake of DNA and/or the protein expressed by dendritic cells triggers immune responses to DNA vaccines.

scholarly journals The Formation of Immunogenic Major Histocompatibility Complex Class II–Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli

2000 ◽  
Vol 191 (6) ◽  
pp. 927-936 ◽  
Author(s):  
Kayo Inaba ◽  
Shannon Turley ◽  
Tomonori Iyoda ◽  
Fumiya Yamaide ◽  
Susumu Shimoyama ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Late Endosomes ◽  
Inflammatory Stimuli ◽  
Peptide Complexes ◽  
Mhc Class Ii Molecules

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.

scholarly journals Syk Tyrosine Kinase and B Cell Antigen Receptor (BCR) Immunoglobulin-α Subunit Determine BCR-mediated Major Histocompatibility Complex Class II–restricted Antigen Presentation

1998 ◽  
Vol 188 (5) ◽  
pp. 819-831 ◽  
Author(s):  
Danielle Lankar ◽  
Volker Briken ◽  
Kristin Adler ◽  
Peter Weiser ◽  
Sylvanie Cassard ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Α Subunit ◽  
Histocompatibility Complex

Stimulation of CD4+ helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-α/Ig-β heterodimers which, second, target antigens to MHC class II–containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-α–associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-α cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide– MHC class II complexes through antigen targeting by BCR subunits.

scholarly journals Survival of Mature CD4 T Lymphocytes Is Dependent on Major Histocompatibility Complex Class II–expressing Dendritic Cells

1997 ◽  
Vol 186 (8) ◽  
pp. 1223-1232 ◽  
Author(s):  
Thomas Brocker
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Close Contact ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Thymic T cell development is controlled by T cell receptor (TCR)–major histocompatibility complex (MHC) interactions, whereas a further dependence of peripheral mature T cells on TCR–MHC contact has not been described so far. To study this question, CD4 T cell survival was surveyed in mice lacking MHC class II expression and in mice expressing MHC class II exclusively on dendritic cells. Since neither of these mice positively select CD4 T cells in the thymus, they were grafted with MHC class II–positive embryonic thymic tissue, which had been depleted of bone marrow derived cells. Although the thymus grafts in both hosts were repopulated with host origin thymocytes of identical phenotype and numbers, an accumulation of CD4+ T cells in peripheral lymphoid organs could only be observed in mice expressing MHC class II on dendritic cells, but not in mice that were completely MHC class II deficient. As assessed by histology, the accumulating peripheral CD4 T cells were found to be in close contact with MHC class II+ dendritic cells, suggesting that CD4 T cells need peripheral MHC class II expression for survival and that class II+ dendritic cells might play an important role for the longevity of CD4 T cells.

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