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At least 19 recordsLinked to original sources
PubMed2000

Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway.

Mycoplasmas and their membranes are potent activators of macrophages, the active principle being lipoproteins and lipopeptides. Two stereoisomers of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 (MALP-2) differing in the configuration of the lipid moiety were synthesized and compared in their macrophage-activating potential, the R-MALP being >100 times more active than the S-MALP in stimulating the release of cytokines, chemokines, and NO. To assess the role of the Toll-like receptor (TLR) family in mycoplasmal lipopeptide signaling, the MALP-2-mediated responses were analyzed using macrophages from wild-type, TLR2-, TLR4-, and MyD88-deficient mice. TLR2- and MyD88-deficient cells showed severely impaired cytokine productions in response to R- and S-MALP. The MALP-induced activation of intracellular signaling molecules was fully dependent on both TLR2 and MyD88. There was a strong preference for the R-MALP in the recognition by its functional receptor, TLR2.

Adaptor Proteins, Signal Transducing↗
PubMed1996

A unique phenylalanine-containing lipopeptide isolated from a rough-colony variant of Mycobacterium avium.

Previous investigations have suggested that the biosynthesis of the Mycobacterium avium serovar-specific glycopeptidolipid antigens involves initial steps that include the participation of lipopeptides. The prevailing assumption is that subsequent glycosylation of those lipopeptides results in the fully glycosylated form of the glycopeptidolipid components. In an effort to identify potential precursors in the biosynthetic pathway of glycopeptidolipid components, we have identified a unique lipopeptide from an M. avium rough variant (MAC702) that was isolated from a patient suffering from a chronic M. avium lung infection. Upon examination it was revealed that although the total lipid extract from MAC702 lacked serovar-specific glycopeptidolipid antigens, it did contain a unique lipopeptide, possessing some amino acids identical to those found in the serovar-specific glycopeptidolipid antigens. Initial examination of acid-hydrolyzed samples of the lipopeptide (lipopeptide-I) revealed the presence of phenylalanine, alanine, and isoleucine, but no carbohydrate. Subsequent mass spectrometric and 1H-NMR and 1H-13C-NMR correlation spectroscopy analysis confirmed the initial results and also revealed the presence of N-methylisoleucine. The following structure for lipopeptide-I was proposed: fatty acyl (C19 or C17)-Phe-N-methyl-Ile-Ile-Phe-Ala-Ile-Ala-Phe. Lipopeptide-I is unlike any heretofore identified compound, however, it does have similar features to lipopeptides previously reported in mycobacteria and fungi. Although its structure does not verify that it is a direct precursor in glycopeptidolipid biosynthesis, the presence of certain components in lipopeptide-I indicate that it may share at least some pathways associated with the biosynthesis of the M. avium serovar-specific glycopeptidolipids.

Amino Acid Sequence↗
PubMed2003

Two human immunodeficiency virus vaccinal lipopeptides follow different cross-presentation pathways in human dendritic cells.

An efficient vaccine against human immunodeficiency virus (HIV) must induce good cellular immune responses. To do this, it must be processed and presented by dendritic cells, which are required for primary T-lymphocyte stimulation. We have previously shown that a model lipopeptide containing a short epitopic peptide from HIV-1 was endocytosed and presented in association with major histocompatibility complex class I molecules by human dendritic cells to specific CD8(+) T lymphocytes, but the cross-presentation pathway needed to be precisely determined. We have studied a longer lipopeptide (Pol(461-484)) and another lipopeptide (Nef(66-97)) currently being used in vaccine trials. Like the shorter lipopeptide, the rhodamine-labeled Pol(461-484) lipopeptide was internalized by endocytosis, as assessed by confocal microscopy. The lipopeptides were processed by dendritic cells and presented to CD8(+) T cells specific for the HLA-A*0201-restricted Pol(476-484) and the HLA-A*0301-restricted Nef(73-82) epitope, respectively. Presentation of both lipopeptides was inhibited by brefeldin A. Presentation of the Pol lipopeptide was inhibited by epoxomycin, a proteasome-specific inhibitor, but not by monensin. This shows that it gained access to the cytosol to be digested by the proteasome. In contrast, presentation of the Nef lipopeptide was not inhibited by epoxomycin but was inhibited by monensin, a classical inhibitor of acid-dependent endosomal enzyme activity, indicating an endocytic processing pathway yielding to major histocompatibility complex class I-restricted presentation. Therefore, the two lipopeptides followed different cross-presentation pathways, both resulting in efficient presentation to CD8(+) T lymphocytes.

AIDS Vaccines↗
PubMed2002

Cell activation by synthetic lipopeptides of the hepatitis C virus (HCV)--core protein is mediated by toll like receptors (TLRs) 2 and 4.

T cell epitopes coupled to a lipid moiety (lipopeptides) may be superior immunostimulants compared to peptide antigens and are currently studied as potential vaccines. The cause of enhanced immunogenicity of lipopeptides is largely unknown but members of the novel family of Toll like receptors (TLR) such as TLR2 and TLR4 have been shown to mediate activation of cells in response to bacterial lipopolysaccharide (LPS) and other lipidated bacterial or viral components. We studied TLR-mediated activation by 14 synthetic lipopeptides corresponding to T cell epitopes on hepatitis C virus (HCV) core in human embryonic kidney cells (HEK293) transiently over-expressing TLR2 and in Ba/F3 mouse bone marrow cells stably transfected with TLR4 and the adaptor molecule MD-2. Stimulation of transfected HEK293 or Ba/F3 cells was measured via luciferase activity as a reporter of nuclear factor kappaB activation. Free peptides, a non-HCV-related lipopeptide as well as LPS and the lipopeptide SK4 were used as controls. Ten of the 14 HCV core lipopeptides stimulated luciferase activity in TLR2-transfected HEK293 cells but not in mock-transfected control cells. Nine of the 14 lipopeptides also stimulated luciferase activity in the TLR4/MD-2 double-transfected Ba/F3 cells but not Ba/F3 control cells. Overall, there was a close statistical correlation between TLR2 and TLR4/MD-2-mediated cell activation by the lipopeptides. In contrast, the corresponding free peptides had no stimulatory effect on TLR2 nor on TLR4/MD-2 transfected cells. Thus, lipopeptides but not their corresponding free peptides can activate cells via TLRs 2 and 4. This activation is apparently affected by the amino acid sequence of the peptide moiety.

Amino Acid Sequence↗
PubMed1993

Lipopeptides activate Gi-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells.

Synthetic lipopeptides activate superoxide-anion (O2-) formation in human neutrophils in a pertussis-toxin (PTX)-sensitive manner, suggesting the involvement of G-proteins of the Gi family in the signal-transduction pathway. We compared G-protein activation by lipopeptides and the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) in dibutyryl-cyclic-AMP-differentiated HL-60 cells. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-SK4 (Pam3AhhSK4) and fMLP activated high-affinity GTPase, i.e. the enzymic activity of G-protein alpha-subunits, in HL-60 membranes in a time- and protein-dependent manner, but they had no effect on Mg(2+)-ATPase and Na+/K(+)-ATPase. Pam3AhhSK4 and fMLP increased Vmax. of GTP hydrolysis. Pam3AhhSK4 activated GTP hydrolysis with half-maximal and maximal effects at about 2 microM and 10 microM respectively. Other lipopeptides activated GTP hydrolysis as well. Lipopeptides were less effective than fMLP to activate GTPase. In membranes from PTX-treated cells, the stimulatory effects of lipopeptides and fMLP on GTPase were abolished. In N-ethylmaleimide-treated membranes, the relative stimulatory effect of Pam3AhhSK4 on GTP hydrolysis was enhanced, whereas that of fMLP was diminished. fMLP and Pam3AhhSK4 activated GTPase in an over-additive manner in N-ethylmaleimide-treated membranes. Unlike fMLP, Pam3AhhSK4 did not enhance incorporation of GTP azidoanilide into, and cholera-toxin-catalysed ADP-ribosylation of Gi-protein alpha-subunits in, HL-60 membranes and did not induce rises in cytosolic Ca2+ concentration. Pam3AhhSK4 and fMLP stimulated phosphatidic acid formation in a PTX-sensitive manner. Pam3AhhSK4 itself did not activate O2- formation, but potentiated the stimulatory effects of fMLP. Our data suggest that (i) lipopeptides activate the GTPase of Gi-proteins, (ii) lipopeptides and fMLP activate Gi-proteins differently, (iii) lipopeptides stimulate phospholipase D via Gi-proteins, and (iv) phosphatidic acid formation is not sufficient for activation of O2- formation.

Adenosine Diphosphate Ribose↗
PubMed1997

Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration.

Macrophages are typically stimulated by components of microbial cell walls. Surprisingly, cell wall-less mycoplasmas can also very efficiently stimulate macrophages. We showed recently that mycoplasma-derived lipopeptides constitute the active principle. We have now isolated a clone of Mycoplasma fermentans expressing mainly one macrophage-stimulating lipopeptide. This lipopeptide was detergent-extracted and isolated by reversed-phase high-performance liquid chromotography, using nitric oxide release from C3H/HeJ mouse macrophages as bioassay for detection. In contrast to "conventional" bacterial lipoproteins, this lipopeptide had a free NH2 terminus. Amino acid composition, sequence, and the molecular weight of 2,163. 3 are consistent with the following structure: S-(2, 3-bisacyloxypropyl)cysteine-GNNDESNISFKEK with one mole C16:0, and a further mole of a mixture of C18:0 and C18:1 fatty acid per lipopeptide molecule. The sequence could not be found in either the protein identification resource nor the Swiss Prot data bank. We named this 2-kD lipopeptide, macrophage-activating lipopeptide-2 (MALP-2). Synthetic dipalmitoyl MALP-2 and mycoplasma-derived MALP-2 were compared with the bioassay. Both lipopeptides showed an identical dose dependency with a half-maximal response at 10(-11) M concentration. MALP-2 may be one of the most potent natural macrophage stimulators besides endotoxin.

Amino Acid Sequence↗
PubMed1999

Lipopeptide particles as the immunologically active component of CTL inducing vaccines.

Using a bipalmitoylated lipopeptide consisting of an ovalbumin helper T-cell epitope covalently linked to an influenza virus cytotoxic T-lymphocyte (CTL) epitope, we addressed possible factors that may be critical for CTL induction. Antigen processing of lipopeptide appears to be required for T-cell induction since there was virtually no in vitro binding of lipopeptide to purified MHC molecules. A major portion of lipopeptide immunogenicity was due to its particulate nature inasmuch as CTL induction in mice correlated with insoluble lipopeptide constructs, whereas more soluble analogs were significantly less immunogenic. Immunohistological analysis of tissue from immunized animals revealed that lipopeptide migration from the s.c. injection site to the spleen could be detected as early as 1 h after immunization and cell-associated lipopeptide was observed on macrophages and dendritic cells, implicating both cell populations in the processing and presentation of lipopeptide particles to CTLs.

Amino Acid Sequence↗
PubMed1998

Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis.

Mycoplasmas are potent macrophage stimulators. We describe the isolation of macrophage-stimulatory lipopeptides S-[2, 3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTDNNSSQSQQPGS GTTNT and S-[2,3-bisacyl(C16:0/C18:0)oxypropyl]cysteinyl-GQTN derived from the Mycoplasma hyorhinis variable lipoproteins VlpA and VlpC, respectively. These lipopeptides were characterized by amino acid sequence and composition analysis and by mass spectrometry. The lipopeptides S-[2,3-bis(palmitoyloxy)propyl]cysteinyl-GQTNT and S-[2, 3-bis(palmitoyloxy)propyl]cysteinyl-SKKKK and the N-palmitoylated derivative of the latter were synthesized, and their macrophage-stimulatory activities were compared in a nitric oxide release assay with peritoneal macrophages from C3H/HeJ mice. The lipopeptides with the free amino terminus showed half-maximal activity at 3 pM regardless of their amino acid sequence; i.e., they were as active as the previously isolated M. fermentans-derived lipopeptide MALP-2. The macrophage-stimulatory activity of the additionally N-palmitoylated lipopeptide or of the murein lipoprotein from Escherichia coli, however, was lower by orders of magnitude. It is concluded that the lack of N-acyl groups in mycoplasmal lipoproteins explains their exceptionally high in vitro macrophage-stimulatory capacity. Certain features that lipopolysaccharide endotoxin and mycoplasmal lipopeptides have in common are discussed. Lipoproteins and lipopeptides are likely to be the main causative agents of inflammatory reactions to mycoplasmas. This may be relevant in the context of mycoplasmas as arthritogenic pathogens and their association with AIDS.

Amino Acid Sequence↗
PubMed1992

Immunization of mice with lipopeptides bypasses the prerequisite for adjuvant. Immune response of BALB/c mice to human immunodeficiency virus envelope glycoprotein.

In vivo priming of CTL requires the association with MHC class I molecules of peptides derived from the processing of endogenously produced proteins. Immunization with exogenous proteins or peptides rarely induces MHC class I-restricted CTL unless they are associated with lipidic compounds. The capacity to induce CTL was compared in synthetic peptides and simple lipopeptides containing the Immunodominant MHC class I H-2Dd-restricted T-cell epitope of HIV-1 gp160. In contrast with free peptides in saline, lipopeptides induced strong primary CTL responses in vivo. These CTL were able to lyse cells infected with a recombinant vaccinia virus expressing the HIV-1 env gene. Priming of CTL was also successful when using 16-amino acid lipopeptides as 34-amino acid lipopeptides, suggesting that several epitopes might be included in a single construct. In vivo priming of CTL also requires CD4+ T cell help. We therefore searched for Th cell activation after priming with lipopeptides. Our results show that, as with CTL induction, Th cell activation with lipopeptides did not require mixing with adjuvant. In addition, lipopeptides were also efficient at stimulating antibody-mediated responses. Our results show that a single lipopeptidic construct can induce a total immune response, which is of importance in vaccine development.

Adjuvants, Immunologic↗
PubMed1991

Intracellular localization of a lipopeptide macrophage activator: immunocytochemical investigations and EELS analysis on ultrathin cryosections of bone marrow-derived macrophages.

Synthetic lipopeptides, structurally derived from the N-terminal part of bacterial lipoprotein, constitute macrophage and B-lymphocyte activators. The molecular mechanism of macrophage activation by lipopeptides still remains unclear. The purpose of our study was to determine the route and kinetics of lipopeptide distribution in bone marrow-derived macrophages. The intracellular localization of the C-terminally biotinylated lipodipeptide Pam3Cys-Ser was investigated on ultrathin cryosections using the biotinstreptavidin-gold system. Our findings indicate that the lipopeptide penetrates the plasma membrane and can already be found within the cytoplasm, the nuclear membrane, and within the nucleus after 2 min of stimulation. The pattern of lipopeptide distribution obtained 2 min after stimulation resembles that obtained after longer incubation times (8 and 20 min). Correlating distribution patterns were observed when using the method of electron energy loss spectroscopy (EELS). These findings are a clear indication for the rapid uptake of lipopeptides into eukaryotic cells, and are of importance for further studies of the immunostimulating properties of the bacterial lipopeptides and vaccines derived therefrom.

Animals↗
PubMed1989

Localization of the cell activator lipopeptide in bone marrow-derived macrophages by electron energy loss spectroscopy (EELS).

Synthetic lipopeptide analogues of bacterial lipoprotein constitute potent polyclonal activators for monocytes/macrophages and B lymphocytes. However, the fate of the lipopeptides after their interaction with target cells is as yet unknown. In order to follow the routes and to determine the distribution of the lipopeptide within macrophages after stimulation, we investigated lipopeptide-stimulated bone marrow-derived macrophages using the novel method of electron energy loss spectroscopy (EELS). Our results show that the lipopeptide was present in different compartments of the cell. The major amount of the activator was located within the cytoplasm and the plasma membrane, and minor quantities were detected within the nuclear membrane and the nucleus. The distribution of the lipopeptides varied depending on the duration of stimulation. Our results should help to elucidate the molecular mechanisms of macrophage stimulation by lipopeptides or other cell activators.

Animals↗
PubMed1997

Synthetic lipopeptides incorporated in liposomes: in vitro stimulation of the proliferation of murine splenocytes and in vivo induction of an immune response against a peptide antigen.

Amphiphilic lipopeptides, such as Pam3CysAlaGly and Pam3CysSerSer, were synthesized and incorporated into liposomes, and their ability to induce the proliferation of BALB/c mouse splenocyte was tested in vitro. When compared to monophosphoryl lipid A (MPL) the following potency order was found: liposomal lipopeptides > liposomal MPL > free (emulsified) lipopeptides. These results strongly depend on the size of the vesicles used: a mitogenic effect was observed only with lipopeptides incorporated within vesicles of diameter < or = 100 nm while lipopeptides in larger vesicles (diameter approximately 300 nm) gave no response. This may be related to the necessity for the liposome-associated lipopeptides to be endocytosed to reach putative intracellular targets. As immunoadjuvanticity seems to be linked to B-lymphocyte activation, the lipopeptides represent attractive alternatives to MPL for the realization of completely synthetic liposome-based peptide vaccine formulations. This was borne out by showing that Pam3CysAlaGly and Pam3CysSerSer, when incorporated in small unilamellar vesicles carrying a covalently conjugated synthetic peptide of sequence IRGERA, corresponding to an epitope of the C-terminal region of histone H3, were able to induce a potent and long-lasting immune response.

Adjuvants, Immunologic↗
PubMed1994

Lipopeptide-polyoxyethylene conjugates as mitogens and adjuvants.

Two lipopeptide analogues of the Escherichia coli lipoprotein rendered water-soluble by polyoxyethylene were tested for mitogenicity in vitro in murine and human B lymphocytes and for adjuvant activity in vivo in mice. These highly amphiphilic lipopeptides retained the biological activity other lipopeptides usually exerted which supports the hypothesis of specific interactions of lipopeptides with membranes of reactive cells. The activation of human B lymphocytes by these lipopeptides was much less pronounced compared to that of murine cells. However, given in combination with anti-CD40 antibodies plus interleukin-4, human B lymphocytes could synergistically be stimulated to proliferate. As an adjuvant, the polyoxyethylene linked lipopeptides were almost as potent as Freund's adjuvants and other basic lipopeptides. Being water-soluble, these novel analogues are easy to apply and they are suitable for field studies as adjuvants when sonication can not usually be provided.

Adjuvants, Immunologic↗
PubMed1992

Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells.

Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration-dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh-Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino-6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys-Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25-dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells.

Blotting, Western↗
PubMed2003

Maturation of bovine dendritic cells by lipopeptides.

The response of DC, and the subsequent stimulation of T cells, is an essential part of the initiation of immune responses following microbial challenge. The response of human DC to bacterial lipopeptides is mediated by toll-like receptor 2, and is characterised by DC maturation and the enhanced capacity to stimulate of T cells. We report here that bovine DC are also induced to mature following lipopeptide stimulation. Exposure of DC to the model lipopeptide Pam3CSK4 was associated with increased expression of MHC, costimulatory molecules, and enhanced secretion of IL-12 and TNFalpha. Lipopeptide-matured DC were superior in their ability to induce T cell activation and IFNgamma secretion. In contrast, exposure of MPhi to lipopeptides induced down-regulation of MHC expression and much lower increases in IL-12 secretion. A lipopeptide derived from the sequence of a relevant mycobacterial lipoprotein, MPB83, also influenced bovine DC by stimulating increases in IL-12 and TNFalpha secretion. These different changes in bovine DC and MPhi may have important implications for immune responses induced following bacterial infection with uptake of microbes by DC resulting in potentiation of their immunostimulatory capacity and uptake by MPhi having a much less marked effect on immune responses.

Adjuvants, Immunologic↗
PubMed1992

Synthetic lipopeptide immunomodulators derived from bacterial lipoprotein: tools for the standardization of in vitro assays.

For the evaluation of immunomodulators by in vitro assays, agents working reproducibly are difficult to obtain; conventional preparations of bacterial immunomodulators tend to vary for different preparations. Here we suggest that synthetic lipopeptide analogues derived from bacterial lipoprotein can be used as standards for various in vitro assays: studying B lymphocyte activation, lipopeptides act as potent mitogens and polyclonal activators inducing immunoglobulin synthesis. In monocytes/macrophages, lipopeptide stimulate the secretion of IL-1, IL-6, tumor necrosis factor (TNF) and nitrogen oxide (NO); they also induce tumor cytotoxicity. Lipopeptides also constitute potent immuno-adjuvants in vitro and in vivo, either in combination with or covalently bound to antigen. These activities are displayed in various species; in mice they are found in LPS non-responder and responder strains. The novel synthetic lipopeptides described here can be synthesized readily in gram amounts with high purity and reproducibility; they are non-toxic and can be stored for a long time even at room temperature. Thus, lipopeptides meet the requirements to serve as effective standards for a multitude of relevant biological assays.

Amino Acid Sequence↗
PubMed2000

Endocytosis of an HIV-derived lipopeptide into human dendritic cells followed by class I-restricted CD8(+) T lymphocyte activation.

CD8(+) T lymphocytes, which are major immune effectors, require primary stimulation by dendritic cells (DC) presenting MHC class I molecule-bound epitopes. Sensitization to exogenous protein epitopes that are not synthesized in DC, such as cross-priming, is obtained through pathways leading to their association with MHC class I. To follow class I-restricted pathways in human DC, we have tracked a lipopeptide derived from the conserved HLA-A*0201-restricted HIV-1 reverse transcriptase 476-484 epitope, by N-terminal addition of an Nepsilon-palmytoyl-lysine. Indeed, lipopeptides elicit cytotoxic responses from CD8(+) T lymphocytes, whereas peptides without a lipid moiety do not. The lipopeptide and its parent peptide were labeled unequivocally by rhodamine to study their entry into immature monocyte-derived human DC by confocal microscopy. The lipid moiety induced endocytosis of the lipopeptide, assessed by rapid entry into vesicles, colocalization with Dextran-FITC and dependence on energy. Internalization occurred even when actin filaments were depolymerized by Cytochalasin B. This internalization induced functional stimulation of specific CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. The peptide alone was not visualized inside the DC and was presented through direct surface association to HLA-A*0201. Therefore, lipopeptides are a unique opportunity to define precisely the pathways that lead exogenous proteins to associate with MHC class I molecules in DC. The results will also be useful to design lipopeptide vaccines.

Antigen Presentation↗