Production of autoreactive I region-restricted T cell hybridomas.

Glimcher, L H; Shevach, Ethan M.

doi:10.1084/jem.156.2.640

Cited by 110 publications

(31 citation statements)

References 12 publications

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“…Upon maturation, DC migrate via the lymphatics to the secondary lymphoid organs and become extremely potent in Ag presentation, but poor in Ag uptake and processing (9 -11). The increase in the Ag presentation ability of mature DC is associated with up-regulation of a variety of molecules, including MHC class II and B7-2, the major triggers for the initiation of T cell activation (35)(36)(37)(38)(39). DC express higher levels of MHC class II and costimulatory molecules than other professional APC.…”

Section: Figurementioning

confidence: 99%

Fascin Is Involved in the Antigen Presentation Activity of Mature Dendritic Cells

Al‐Alwan

Rowden

Lee

et al. 2001

The Journal of Immunology

123

111

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Maturation of dendritic cells (DC) is critical to their development into potent APCs. Upon maturation, DC up-regulate the expression of MHC class II as well as costimulatory and adhesion molecules, all of which are important in Ag presentation. In addition, they undergo structural changes characterized by the expression of numerous long dendrites. Fascin is an actin-bundling protein that has been reported to be important for the development of dendrites. In this study, we evaluated fascin expression and function during DC maturation into potent APC. In vitro, treatment of bone marrow-derived DC (BM-DC) with GM-CSF resulted in increased levels of fascin expression. This increase correlated directly with an increase in MHC class II and B7-2 expression. Fascin expression was decreased by the addition of TGF-β and increased by the addition TNF-α to the culture. These cytokines suppress or enhance DC maturation, respectively. Increased levels of fascin expression were found to correlate with increased APC activity in a one-way MLR. Specific inhibition of fascin expression, using antisense oligonucleotides, markedly reduced this APC allostimulatory activity. These data demonstrate that fascin expression correlates with DC maturation into APC, and it plays a significant role in the ability of DC to function as APC. This observation is the first evidence linking fascin-mediated dendrite formation with the APC activity of DC.

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Section: Figurementioning

confidence: 99%

Fascin Is Involved in the Antigen Presentation Activity of Mature Dendritic Cells

Al‐Alwan

Rowden

Lee

et al. 2001

The Journal of Immunology

123

111

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“…Four hybridomas that react to three different HEL peptides have been used: A2.A2 (HEL 46 -61 ), 2B6.3 (HEL [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] ), 3B11.1 (HEL 34 -45 ), and 3A9 (HEL 46 -61 ). Figs.…”

Section: Presentation Of Mhc Ii-restricted Endogenous Hel Is Tap Indementioning

confidence: 99%

Presentation of Endogenously Synthesized MHC Class II-Restricted Epitopes by MHC Class II Cancer Vaccines Is Independent of Transporter Associated with Ag Processing and the Proteasome

Dissanayake

Tuera

Ostrand‐Rosenberg

2005

The Journal of Immunology

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Cell-based vaccines consisting of invariant chain-negative tumor cells transfected with syngeneic MHC class II (MHC II) and costimulatory molecule genes are prophylactic and therapeutic agents for the treatment of murine primary and metastatic cancers. Vaccine efficacy is due to direct presentation of endogenously synthesized, MHC II-restricted tumor peptides to CD4+ T cells. Because the vaccine cells lack invariant chain, we have hypothesized that, unlike professional APC, the peptide-binding groove of newly synthesized MHC II molecules may be accessible to peptides, allowing newly synthesized MHC II molecules to bind peptides that have been generated in the proteasome and transported into the endoplasmic reticulum via the TAP complex. To test this hypothesis, we have compared the Ag presentation activity of multiple clones of TAP-negative and TAP-positive tumor cells transfected with I-Ak genes and the model Ag hen egg white lysozyme targeted to the endoplasmic reticulum or cytoplasm. Absence of TAP does not diminish Ag presentation of three hen egg white lysozyme epitopes. Likewise, cells treated with proteasomal and autophagy inhibitors are as effective APC as untreated cells. In contrast, drugs that block endosome function significantly inhibit Ag presentation. Coculture experiments demonstrate that the vaccine cells do not release endogenously synthesized molecules that are subsequently endocytosed and processed in endosomal compartments. Collectively, these data indicate that vaccine cell presentation of MHC II-restricted endogenously synthesized epitopes occurs via a mechanism independent of the proteasome and TAP complex, and uses a pathway that overlaps with the classical endosomal pathway for presentation of exogenously synthesized molecules.

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“…To become susceptible to IL-1 activity, the IL-2 producer T cell needs to interact with Ia antigens (8,11,12). Under appropriate culture conditions, autologous Ia antigens by themselves induce T cells to express receptors for IL-2 (13), to produce IL-2 (12)(13)(14)(15)(16), and thereby to proliferate (13)(14)(15)(16)(17)(18). These observations raise the question of whether, besides serving as restricting elements for foreign antigens, Ia antigens could also function as signalling channels between T cells and Ia-bearing cells.…”

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confidence: 99%

Monoclonal antibodies against human Ia antigens stimulate monocytes to secrete interleukin 1.

Palacios¹

1985

Proc. Natl. Acad. Sci. U.S.A.

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The monoclonal antibodies (mAb) DA6.147, DA6.164, and HIG.48 against human Ia antigens, but not the W6/32 mAb against human class I major histocompatibility complex antigens or the anti-monocyte OKM1 and 63D3 mAb, stimulated monocytes to secrete interleukin 1 (IL-1). IL-1 was measured by its property of promoting the production of interleukin 2 (IL-2) by phytohemagglutinin-treated LBRM-33 clone 1A5 cells. IL-1 activity induced by anti-Ia antibodies could be detected 24 hr after initiation of the cultures and reached its highest levels at days 3-4 of culture. Concentrations of 1 jig/ml or higher of the anti-Ia antibodies induced monocytes to secrete significant levels of IL-1 activity. The anti-Ia mAb induced Ia-bearing but not Ia-negative monocytes to secrete IL-1. Both Ia-positive and Ia-negative monocytes produced IL-1 activity under the stimulus of lipopolysaccharide. It is concluded that the DA6.147, DA6.164, and HIG.48 mAb stimulate secretion of IL-1 by interacting Ia antigens on monocytes. The data support the view that besides serving as restricting elements for recognition of foreign antigens by T cells, Ia antigens may also function as transducer elements.Class II genes of the major histocompatibility complex (MHC) code for developmentally regulated polymorphic cell-surface glycoproteins, the Ia antigens (reviewed in refs.

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Production of autoreactive I region-restricted T cell hybridomas.

Cited by 110 publications

References 12 publications

Fascin Is Involved in the Antigen Presentation Activity of Mature Dendritic Cells

Fascin Is Involved in the Antigen Presentation Activity of Mature Dendritic Cells

Presentation of Endogenously Synthesized MHC Class II-Restricted Epitopes by MHC Class II Cancer Vaccines Is Independent of Transporter Associated with Ag Processing and the Proteasome

Monoclonal antibodies against human Ia antigens stimulate monocytes to secrete interleukin 1.

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