Vitamin C Up-regulates Expression of CD80, CD86 and MHC Class II on Dendritic Cell Line, DC-1 Via the Activation of p38 MAPK

Dendritic cells (DC) can provide all the known costimulatory signals required for activation of unprimed T cells and are the most efficient and perhaps the critical antigen presenting cells in the induction of primary T cell-mediated immune responses. It is now shown that mouse cell lines with many of the features of DC can be generated using the MIB phi 2-N11 retroviral vector transducing a novel envAKR-mycMH2 fusion gene. The immortalized dendritic cell line (CB1) displays most of the morphologic, immunophenotypic, and functional attributes of DC, including constitutive expression of major histocompatibility complex (MHC) class II molecules, costimulatory molecules B7/BB1, heat stable antigen, intracellular adhesion molecule 1, and efficient antigen-presenting ability. Granulocyte/macrophage colony-stimulating factor (GM-CSF) proved to be effective in increasing MHC class II molecule expression and in enhancing presentation of native protein antigens. In comparison with macrophages, CB1 dendritic cells did not exhibit phagocytic and chemotactic activity in response to various stimuli and lipopolysaccharide activation was ineffective in inducing tumor necrosis factor alpha or interleukin 1 beta production. CB1 cells, pulsed with haptens in vitro and injected into naive mice were able to induce delayed-type hypersensitivity responses, further increased with pretreatment with GM-CSF, indicating that these cells may represent an immature, rather than a mature DC. The ability of CB1 to prime T cells in vivo could provide a tool to design novel immunization strategies.

Download Full-text

Faculty Opinions recommendation of Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1009216.121260 ◽

2002 ◽

Author(s):

Tim Elliott

Keyword(s):

Plasma Membrane ◽

Dendritic Cell ◽

Mhc Class Ii ◽

Class Ii ◽

Dendritic Cell Maturation ◽

Cell Maturation

Download Full-text

Faculty Opinions recommendation of Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13364975.14735081 ◽

2011 ◽

Author(s):

Jacques Zimmer

Keyword(s):

T Cells ◽

Dendritic Cell ◽

Nk Cells ◽

Natural Killer ◽

Mhc Class Ii ◽

Cd4 T Cells ◽

Class Ii ◽

Cell Interactions

Download Full-text

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

Molecular Biology of the Cell ◽

10.1091/mbc.e02-11-0744 ◽

2003 ◽

Vol 14 (8) ◽

pp. 3378-3388 ◽

Cited By ~ 36

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.

Download Full-text

MHC Class II Ubiquitination Regulates Dendritic Cell Function and Immunity

The Journal of Immunology ◽

10.4049/jimmunol.2001426 ◽

2021 ◽

pp. ji2001426

Author(s):

Kayla R. Wilson ◽

Devi Jenika ◽

Annabelle B. Blum ◽

Christophe Macri ◽

Bangyan Xu ◽

...

Keyword(s):

Dendritic Cell ◽

Mhc Class Ii ◽

Cell Function ◽

Class Ii ◽

Dendritic Cell Function

Download Full-text

Small amounts of superantigen, when presented on dendritic cells, are sufficient to initiate T cell responses.

Journal of Experimental Medicine ◽

10.1084/jem.178.2.633 ◽

1993 ◽

Vol 178 (2) ◽

pp. 633-642 ◽

Cited By ~ 91

Author(s):

N Bhardwaj ◽

J W Young ◽

A J Nisanian ◽

J Baggers ◽

R M Steinman

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Dendritic Cell ◽

Mhc Class Ii ◽

Cell Receptor ◽

Class Ii ◽

Cell Mediated Immunity ◽

Quiescent T Cells ◽

Antigen Presenting

Dendritic cells are potent antigen-presenting cells for several primary immune responses and therefore provide an opportunity for evaluating the amounts of cell-associated antigens that are required for inducing T cell-mediated immunity. Because dendritic cells express very high levels of major histocompatibility complex (MHC) class II products, it has been assumed that high levels of ligands bound to MHC products ("signal one") are needed to stimulate quiescent T cells. Here we describe quantitative aspects underlying the stimulation of human blood T cells by a bacterial superantigen, staphylococcal enterotoxin A (SEA). The advantages of superantigens for quantitative studies of signal one are that these ligands: (a) engage MHC class II and the T cell receptor but do not require processing; (b) are efficiently presented to large numbers of quiescent T cells; and (c) can be pulsed onto dendritic cells before their application to T cells. Thus one can relate amounts of dendritic cell-associated SEA to subsequent lymphocyte stimulation. Using radioiodinated SEA, we noted that dendritic cells can bind 30-200 times more superantigen than B cells and monocytes. Nevertheless, this high SEA binding does not underlie the strong potency of dendritic cells to present antigen to T cells. Dendritic cells can sensitize quiescent T cells, isolated using monoclonals to appropriate CD45R epitopes, after a pulse of SEA that occupies a maximum of 0.1% of surface MHC class II molecules. This corresponds to an average of 2,000 molecules per dendritic cell. At these low doses of bound SEA, monoclonal antibodies to CD3, CD4, and CD28 almost completely block T cell proliferation. In addition to suggesting new roles for MHC class II on dendritic cells, especially the capture and retention of ligands at low external concentrations, the data reveal that primary T cells can generate a response to exceptionally low levels of signal one as long as these are delivered on dendritic cells.

Download Full-text