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.
Antigen Presentation ; Cytosol ; Dendritic Cells ; Perylene ; Quinones

Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.
Antigen Presentation* ; Dendritic Cells ; Dexamethasone* ; Macrophages ; Ovalbumin ; Ovum ; T-Lymphocytes

Antigen Presentation ; Asthma ; blood ; etiology ; therapy ; Eosinophils ; physiology ; Humans

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.
Animals ; Antigen Presentation* ; Antigen-Presenting Cells ; Immune System ; Immunotherapy ; Metformin* ; Mice ; Ovum

MHC class II has long been known to play a classical role in antigen presentation and to act as a signal transducer capable of inducing the adaptive immunity needed to produce pathogen specific antibodies. However, it has recently been revealed that MHC class II can also promote the activation of Toll-like receptor mediated signaling by functioning as an adapter. This means that in addition to its classical function of adaptive immunity, MHC class II also plays an intriguing role in the mechanisms that regulate innate immunity. That being the case, queries inevitably arise regarding the fact that many pathogens have tried to control the induction of MHC class II so as to escape the host immune response. Liu et al (Nat Immunol 2011;12:416-424) demonstrated that intracellular MHC class II interacted with Btk, and that this activated Btk promoted TLR signaling via Myd88 and TRIF. The results of this study provide insight regarding the possibility of a novel role for MHC class II, which was heretofore regarded solely as a classical molecule involved in adaptive immune responses, as a regulator of innate immune responses.
Adaptive Immunity ; Antibodies ; Antigen Presentation ; Immunity, Innate ; Toll-Like Receptors ; Transducers ; United Nations

OBJECTIVES: The genes for transporters associated with antigen processing (TAP) are located near to HLA class II coding regions and related to antigen presentation. Therefore polymorphisms of TAP might alter the T-cell mediated immune response and influence susceptibility to schizophrenia, which is known to have alterations in T-cell immunity. The aim of this study was to verify the relationship between schizophrenia and polymorphisms of TAP2 genes. METHODS: 257 patients with schizophrenia and 184 normal controls participated in this study. TAP2 polymorphic residues at positions 379, 565 and 665 were typed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and single-strand conformation polymorphism (SSCP). The resulted products, TAP2379, TAP2565 and TAP2665 were assessed. RESULTS: The frequency of TAP2 alleles did not differ between patients with schizophrenia and controls. The polymorphic sites TAP2379, TAP2565 and TAP2665 did not show any difference in their amino acid substitution frequencies. CONCLUSION: This study did not show the association of the TAP2 gene with schizophrenia in Korean population. Further studies are needed to test the informative value of haplotypes including other polymorphic sites.
Alleles ; Amino Acid Substitution ; Antigen Presentation ; Clinical Coding ; Haplotypes ; Humans ; Schizophrenia* ; T-Lymphocytes

BACKGROUND: It is known that HLA molecule can restrict specific IgE responses, but few studies have documented the association between HLA and sensitization to house dust mite(HDM). OBJECTIVE: To evaluate whether a specific HLA type can be a risk or protective factor for the development of HDM sensitivity. METHOD: Total 146 subjects were genotyped for HLA-DRB1 using PCR-SSP technique and HDM sensitivity, determined by skin prick test using two mite allergens, D. pteronyssinus (Dp) and D. farinae (Df). Subjects were grouped according to Dp or Df sensitivity and linkage analysis between HDM sensitivity and HLA-DRB1 genotype was performed. RESULTS: The data revealed higher allele frequencies of DRB1*07 in Dp or Df sensitive groups compared to insensitive groups (11.6% vs. 2.6% in Dp, 11.5% vs. 3.3% in Df group, p<0.05), but the other allele frequencies showed no difference. CONCLUSION: There was a significant association between HLA-DRB1*07 genotype and HDM sensitization. These results indicate that antigen presentation by HLA class II molecule restricts the development of specific IgE response to HDM.
Allergens ; Antigen Presentation ; Dust* ; Gene Frequency ; Genotype* ; HLA-DRB1 Chains* ; Immunoglobulin E ; Mites ; Pyroglyphidae* ; Skin

Antigen processing (TAP, HLA-DM and LMP) genes map within the major histocompatibility complex (MHC) class II region between the HLA-DQB1 and -DPB1 loci, and are involved in the processing of peptides bound to HLA class I or class II molecules. In order to determine the allele frequencies of antigen processing genes and the various linkage disequilibria existing among these genes, we have analyzed TAP1, TAP2, HLA-DMA, and HLA-DMB, LMP2, LMP7 polymorphisms in 184 unrelated healthy Koreans using the rnethod of PCR-SSCP, ARMS-PCR and PCR-RFLP. The frequencies of antigen processing genes were TAP1A (77.7%), TAP1*B (17.1%), TAP1*C (5.2%), TAP2*A (41.6%), TAP2*B (31.3%), TAP2*C (3.3%), TAP2*D (0.8%), TAP2*E (6.5%), TAP2*G (0.8%), HLA-DMA*0101 (81.5%), HLA-DMA*0102 (18.2%), HLA-DMA*0103 (0.3%), HLA-DMB*0101 (42.9%), HLA-DMB*0102 (19.0%), HLA-DMB*0103 (38.0%), LMP2*R (78.8%), LMP2*H (21.2%), LMP7*A (35.3%), LMP7*B (56.0%), LMP7*C (4.9%), and LMP7*D (3.8%). We also analysed two- locus association among each locus. Many significant positive associations were observed between these two loci, such as between HLA-DMB and TAP1, between HLA-DMA and HLA-DMB, between LMP2 and LMP7, and between TAP1 and LMP7. Conversely, any significant linkage disequilibrium was not detected between HLA-DMB and LMP2. These results could be used as control data for disease association and population genetics studies in Korean population.
Antigen Presentation* ; Gene Frequency ; Genetics, Population ; Linkage Disequilibrium ; Major Histocompatibility Complex ; Peptides

PURPOSE: Protein cages are promising nanoplatform candidates for efficient delivery systems due to their homogenous size and structure with high biocompatibility and biodegradability. In this study, we investigate the potential of lumazine synthase protein cage as an antigen delivery system to dendritic cells (DCs), which induce antigen-specific T cell proliferation. MATERIALS AND METHODS: Ovalbumin (OVA) peptides OT-1 (SIINFEKL) and OT-2 (ISQAVHAAHAEINEAGR) were genetically inserted to lumazine synthase and each protein cage was over-expressed in Escherichia coli as a soluble protein. The efficiency of antigen delivery and the resulting antigen-specific T cell proliferation by DCs was examined in vitro as well as in vivo. RESULTS: We successfully generated and characterized OVA peptides carrying lumazine synthase protein cages. The OT-1 and OT-2 peptides carried by lumazine synthases were efficiently delivered and processed by DCs in vitro as well as in vivo, and induced proliferation of OT-1-specific CD8+T cells and OT-2-specific CD4+T cells. CONCLUSION: Our data demonstrate the potential of lumazine synthase protein cage being used as a novel antigen delivery system for DC-based vaccine development in future clinical applications.
Antigen Presentation ; Cell Proliferation ; Dendritic Cells ; Escherichia coli ; Nanoparticles* ; Ovalbumin ; Ovum ; Peptides ; Vaccines

Superantigens are potent immunostimulatory exotoxins well known to be produced by Staphylococcus aureus (S. aureus). These exotoxins have capacity to act as superantigens by binding with the variable beta(Vbeta) region of lymphocytes in chronic rhinosinusitis with nasal polyposis, bypassing normal antigen processing and directly stimulating a massive inflammatory response. Accumulated evidence is now convincing that S. aureus superantigens may play an important role in development of chronic rhinosinusitis with nasal polyposis which are thought to skew the cytokine response towards a Th2 phenotype inducing eosinophilia and the production of polycolonal IgE. This review summarizes the current evidence of characteristics and its role superantigens in pathophysiology of nasal polyposis.
Antigen Presentation ; Eosinophilia ; Exotoxins ; Immunoglobulin E ; Lymphocytes ; Nasal Polyps ; Phenotype ; Staphylococcus aureus ; Superantigens