Immune Netw.  2011 Dec;11(6):412-415. 10.4110/in.2011.11.6.412.

Immunomodulatory Effects of Hypocrellin A on MHC-restricted Antigen Processing

• Park S
• Im SA
• Kim KH
• Lee CK

• KMID: 2150728
• DOI: http://doi.org/10.4110/in.2011.11.6.412

Abstract

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the H-2K(b)-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

Keyword

Hypocrellin A; MHC-restricted antigen presentation; Immunomodulator

MeSH Terms

Antigen Presentation
Cytosol
Dendritic Cells
Perylene
Quinones
Perylene
Quinones

Figure

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  Figure 1 Effects of hypocrellin A on the MHC-restricted presentation of exogenous OVA. (A) DC2.4 cells were incubated with the indicated amounts of hypocrellin A for 2 h, and then biodegradable microspheres containing OVA (50µg/ml as OVA) were added to the cultures for 2 h. The cells were then fixed with paraformaldehyde, and the amounts of OVA peptides presented on MHC class I molecules were assessed by a LacZ T cell activation assay using OVA-specific CD8 T cell hybridoma B3Z cells. (B) BM-DCs generated from bone marrow cells of BALB/c mice were incubated with the indicated amounts of hypocrellin A for 2 h, and then biodegradable microspheres containing OVA (50µg/ml as OVA) were added to the cultures for 2 h. The cells were then washed, fixed with paraformaldehyde, and the amounts of OVA peptides presented on MHC class II molecules were assessed using OVA-specific CD4 T cell hybridoma DOBW cells.

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  Figure 2 Effects of hypocrellin A on the cytosolic pathway of endogenous antigen presentation. (A) DC2.4 cells were incubated with the indicated amounts of hypocrellin A for 2 h, washed, and then soluble OVA was loaded into cytosol by osmotic shock as described previously (13). After 2-h incubation, the amounts of H-2Kb-OVA peptide complexes were assessed using OVA-specific CD8 T cell hybridoma B3Z cells. (B) The indicated amounts of hypocrellin A were added to cultures of DC2.4 cells that had been infected with rVV-OVA (MOI 10). After 6 h, the DCs were washed, fixed with paraformaldehyde, and then the capacity to activate OVA-specific CD8 T cells was assessed using OVA-specific CD8 T cell hybridoma B3Z cells.

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  Figure 3 Hypocrellin A does not inhibit the expression levels of class I and class II MHC molecules or the presentation of a synthetic OVA peptide SIINFEKL. Hypocrellin A (2,000 nM) was added to cultures of DC2.4 cells for 2 h. The cells were harvested, washed, and then stained with anti-mouse H-2Kb monoclonal antibody (A) or anti-I-Ab monoclonal antibody (B). The shaded histograms represent the expression levels of class I and class II MHC molecules in the presence of hypocrellin A, and the thick lines represent the expression levels of class I and class II MHC molecules in the absence of hypocrellin A. The dotted lines represent isotype controls. (C) Indicated amounts of hypocrellin A were added to cultures of DC2.4 cells together with the antigenic peptide of OVA, SIINFEKL. The cells were harvested, washed, and then the amount of SIINFEKL-H-2Kb complex was measured by a LacZ T cell activation assay using OVA-specific CD8 T cell hybridoma B3Z cells.

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