Enhanced delivery of exogenous peptides into the class I antigen processing and presentation pathway.

Abstract:

:Current immunization strategies, using peptide or protein antigens, generally fail to elicit cytotoxic-T-lymphocyte responses, since these antigens are unable to access intracellular compartments where loading of major histocompatibility complex class I (MHC-I) molecules occurs. In an attempt to circumvent this, we investigated whether the GM1 receptor-binding B subunit of Escherichia coli heat-labile toxin (EtxB) could be used to deliver class I epitopes. When a class I epitope was conjugated to EtxB, it was delivered into the MHC-I presentation pathway in a GM1-binding-dependent fashion and resulted in the appearance of MHC-I-epitope complexes at the cell surface. Importantly, we show that the efficiency of EtxB-mediated epitope delivery could be strikingly enhanced by incorporating, adjacent to the class I epitope, a 10-amino-acid segment from the C terminus of the DNA polymerase (Pol) of herpes simplex virus. The replacement of this 10-amino-acid segment by a heterologous sequence or the introduction of specific amino acid substitutions within this segment either abolished or markedly reduced the efficiency of class I epitope delivery. If the epitope was extended at its C terminus, EtxB-mediated delivery into the class I presentation pathway was found to be completely dependent on proteasome activity. Thus, by combining the GM1-targeting function of EtxB with the 10-amino-acid Pol segment, highly efficient delivery of exogenous epitopes into the endogenous pathway of class I antigen processing and presentation can be achieved.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

De Haan L,Hearn AR,Rivett AJ,Hirst TR

doi

10.1128/iai.70.6.3249-3258.2002

keywords:

subject

Has Abstract

pub_date

2002-06-01 00:00:00

pages

3249-58

issue

6

eissn

0019-9567

issn

1098-5522

journal_volume

70

pub_type

杂志文章
  • Effects of the composition of peritoneal dialysis fluid on chemiluminescence, phagocytosis, and bactericidal activity in vitro.

    abstract::Commercial fluid used for peritoneal lavage in peritonitis and in peritoneal dialysis suppressed the activity of peripheral blood leukocytes as measured by chemiluminescence, phagocytosis, and bacterial killing. Suppression was found to be due to the low pH and high osmolality of the fluid. The pH was adjusted to noni...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.33.1.130-135.1981

    authors: Duwe AK,Vas SI,Weatherhead JW

    更新日期:1981-07-01 00:00:00

  • Etiology of chronic pneumonia in rats and a study of the experimental disease in mice.

    abstract::The lungs of conventional rats with chronic pneumonia contained Streptobacillus moniliformis and Mycoplasma pulmonis. These organisms singly and in combination failed to produce lung disease when inoculated into specific pathogen-free rats. On the other hand, diseased lung homogenate not containing cultivable organism...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.6.1.83-91.1972

    authors: Gay FW,Maguire ME,Baskerville A

    更新日期:1972-07-01 00:00:00

  • Antibody to virus components in volunteers experimentally infected with human coronavirus 229E group viruses.

    abstract::Antibody rises to various virus subcomponents were measured by enzyme-linked immunosorbent assay in the paired sera of volunteers experimentally infected with human coronavirus 229E group viruses. Most of the antibody made during infection was directed against the virus surface projections, with only small amounts of ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.31.3.845-849.1981

    authors: Macnaughton MR,Hasony HJ,Madge MH,Reed SE

    更新日期:1981-03-01 00:00:00

  • Immunoglobulin G and M composition of naturally occurring antibody to type III group B streptococci.

    abstract::Human sera were examined by an enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgM antibodies to purified type III polysaccharide of group B streptococci. The antigen-binding capacity of a reference human serum was determined by a radioimmunoassay, and the total antibody content was determined by quan...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.46.1.98-104.1984

    authors: Anthony BF,Concepcion NF,Wass CA,Heiner DC

    更新日期:1984-10-01 00:00:00

  • Burkholderia (basonym Pseudomonas) cepacia binding to lipid receptors.

    abstract::Piliated Burkholderia (formerly Pseudomonas) cepacia from sputa of cys tic fibrosis patients in Toronto, Canada, were shown earlier to bind to purified mucins and to a protein receptor on epithelial cells via a 22-kDa adhesin located on unique cable pili. However, a second receptor, thought to be lipid in nature, was ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.64.4.1420-1425.1996

    authors: Sylvester FA,Sajjan US,Forstner JF

    更新日期:1996-04-01 00:00:00

  • Antibody response to successive booster doses of tetanus toxoid in adults.

    abstract::A study of the rise and fall in circulating tetanus antitoxin in a group of 15 adults after basic and booster immunization indicates that although individuals vary greatly in their responsiveness to toxoid, the falloff in antitoxin appears to be fractionally constant for each individual, and over periods of 5 to 6 yea...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.10.1.1-5.1974

    authors: Trinca JC

    更新日期:1974-07-01 00:00:00

  • Histophilus somni IbpA DR2/Fic in virulence and immunoprotection at the natural host alveolar epithelial barrier.

    abstract::Newly recognized Fic family virulence proteins may be important in many bacterial pathogens. To relate cellular mechanisms to pathogenesis and immune protection, we studied the cytotoxicity of the Histophilus somni immunoglobulin-binding protein A (IbpA) direct repeat 2 Fic domain (DR2/Fic) for natural host target cel...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.01277-09

    authors: Zekarias B,Mattoo S,Worby C,Lehmann J,Rosenbusch RF,Corbeil LB

    更新日期:2010-05-01 00:00:00

  • Antibody-independent interaction of the first component of complement with Gram-negative bacteria.

    abstract::The interaction of the first component of complement with two serum-sensitive strains of Escherichia coli and Klebsiella pneumoniae was studied. It could be demonstrated that highly purified C1, free of immunoglobulin G and immunoglobulin M, binds to E. coli or K. pneumoniae. C1 binding was also found with specificall...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.22.1.5-9.1978

    authors: Loos M,Wellek B,Thesen R,Opferkuch W

    更新日期:1978-10-01 00:00:00

  • Streptolysin S inhibits neutrophil recruitment during the early stages of Streptococcus pyogenes infection.

    abstract::In contrast to infection of superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and suppress inflammation. To examine this, we analyzed the behavior of an S. pyogen...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00420-09

    authors: Lin A,Loughman JA,Zinselmeyer BH,Miller MJ,Caparon MG

    更新日期:2009-11-01 00:00:00

  • Genetic analysis of the 9.5-kilobase virulence plasmid of Yersinia pestis.

    abstract::The 9.5-kilobase plasmid of Yersinia pestis determines plasminogen activator, coagulase, pesticin, and pesticin immunity activities. We have mapped and cloned the loci encoding these activities and demonstrated that both plasminogen activator and coagulase were determined by the same gene, designated pla. The primary ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.10.2743-2748.1988

    authors: Sodeinde OA,Goguen JD

    更新日期:1988-10-01 00:00:00

  • Vaginolysin drives epithelial ultrastructural responses to Gardnerella vaginalis.

    abstract::Gardnerella vaginalis, the bacterial species most frequently isolated from women with bacterial vaginosis (BV), produces a cholesterol-dependent cytolysin (CDC), vaginolysin (VLY). At sublytic concentrations, CDCs may initiate complex signaling cascades crucial to target cell survival. Using live-cell imaging, we obse...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00627-13

    authors: Randis TM,Zaklama J,LaRocca TJ,Los FC,Lewis EL,Desai P,Rampersaud R,Amaral FE,Ratner AJ

    更新日期:2013-12-01 00:00:00

  • Constitutive expression of outer surface protein C diminishes the ability of Borrelia burgdorferi to evade specific humoral immunity.

    abstract::The Lyme disease spirochete Borrelia burgdorferi reduces the expression of outer surface protein C (OspC) in response to the development of an anti-OspC humoral response, leading to the hypothesis that the ability to repress OspC expression is critical for the pathogen to proceed to chronic infection. B. burgdorferi w...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00713-06

    authors: Xu Q,Seemanapalli SV,McShan K,Liang FT

    更新日期:2006-09-01 00:00:00

  • Capsular polysaccharide is a major complement resistance factor in lipopolysaccharide O side chain-deficient Klebsiella pneumoniae clinical isolates.

    abstract::We have previously demonstrated the existence of Klebsiella pneumoniae clinical isolates deficient in the lipopolysaccharide O side chain, the major factor for resistance to complement-mediated killing in this bacterial species. These isolates are complement resistant, and their mechanisms to resist complement were in...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.2.953-955.2000

    authors: Alvarez D,Merino S,Tomás JM,Benedí VJ,Albertí S

    更新日期:2000-02-01 00:00:00

  • Reactivation of latent Herpes simplex virus after pneumococcal pneumonia in mice.

    abstract::In attempts to reactivate latent herpes simplex virus, we instilled Diplococcus pneumoniae intratracheally into mice harboring latent infections in sacrosciatic spinal ganglia. All mice developed a severe pneumonia within 24 h and were given penicillin therapy. Representative mice that survived the penumonia were sacr...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.11.4.635-639.1975

    authors: Stevens JG,Cook ML,Jordan MC

    更新日期:1975-04-01 00:00:00

  • C2 toxicity in extract of Clostridium botulinum type C spores.

    abstract::Toxic protein(s) neutralized with anti-C2 toxic serum was extracted from Clostridium botulinum type C spores treated with an alkaline mercaptoethanol solution. C2 toxicity in the spores was located in the spore coat fraction and was more heat stable than that found in culture fluid. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.41.2.858-860.1983

    authors: Yamakawa K,Nishida S,Nakamura S

    更新日期:1983-08-01 00:00:00

  • The two variants of the Streptococcus pneumoniae pilus 1 RrgA adhesin retain the same function and elicit cross-protection in vivo.

    abstract::Thirty percent of Streptococcus pneumoniae isolates contain pilus islet 1, coding for a pilus composed of the backbone subunit RrgB and two ancillary proteins, RrgA and RrgC. RrgA is the major determinant of in vitro adhesion associated with pilus 1, is protective in vivo in mouse models, and exists in two variants (c...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00601-10

    authors: Moschioni M,Emolo C,Biagini M,Maccari S,Pansegrau W,Donati C,Hilleringmann M,Ferlenghi I,Ruggiero P,Sinisi A,Pizza M,Norais N,Barocchi MA,Masignani V

    更新日期:2010-12-01 00:00:00

  • Transient expression of RhoA, -B, and -C GTPases in HeLa cells potentiates resistance to Clostridium difficile toxins A and B but not to Clostridium sordellii lethal toxin.

    abstract::The bacterial pathogen Clostridium difficle synthesizes two high-molecular-weight toxins (A and B), which exhibit toxic effects in vivo and in vitro. Here, we present evidence that the major intracellular targets of these two toxins are the Rho GTPases. Overexpression of RhoA, RhoB, or RhoC GTPases in transfected HeLa...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.63.10.4063-4071.1995

    authors: Giry M,Popoff MR,von Eichel-Streiber C,Boquet P

    更新日期:1995-10-01 00:00:00

  • Synergistic and additive effects of chromosomal and plasmid-encoded hemolysins contribute to hemolysis and virulence in Photobacterium damselae subsp. damselae.

    abstract::Photobacterium damselae subsp. damselae causes infections and fatal disease in marine animals and in humans. Highly hemolytic strains produce damselysin (Dly) and plasmid-encoded HlyA (HlyA(pl)). These hemolysins are encoded by plasmid pPHDD1 and contribute to hemolysis and virulence for fish and mice. In this study, ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00155-13

    authors: Rivas AJ,Balado M,Lemos ML,Osorio CR

    更新日期:2013-09-01 00:00:00

  • The acylated form of protein D of Haemophilus influenzae is more immunogenic than the nonacylated form and elicits an adjuvant effect when it is used as a carrier conjugated to polyribosyl ribitol phosphate.

    abstract::The nonacylated form of protein D (PDm) of Haemophilus influenzae has been shown to induce the production of antibodies that are bactericidal to homologous and heterologous nontypeable H. influenzae (NTHi) strains. In this study, immunization of rats with lipoprotein D (LPD) induced higher levels of anti-protein D imm...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.65.12.5010-5016.1997

    authors: Akkoyunlu M,Melhus A,Capiau C,van Opstal O,Forsgren A

    更新日期:1997-12-01 00:00:00

  • A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma gondii infection.

    abstract::Protective immunity against Toxoplasma gondii is known to be mediated mainly by T lymphocytes and gamma interferon (IFN-gamma). The contribution of CD4(+) and CD8(+) T-lymphocyte subsets to protective immune responses against T. gondii infection, triggered by a GRA1 (p24) DNA vaccine, was assessed in this study. In vi...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.71.1.309-316.2003

    authors: Scorza T,D'Souza S,Laloup M,Dewit J,De Braekeleer J,Verschueren H,Vercammen M,Huygen K,Jongert E

    更新日期:2003-01-01 00:00:00

  • Cholera toxin impairs the differentiation of monocytes into dendritic cells, inducing professional antigen-presenting myeloid cells.

    abstract::Cholera toxin (CT) is a potent adjuvant for mucosal vaccination; however, its mechanism of action has not been clarified completely. It is well established that peripheral monocytes differentiate into dendritic cells (DCs) both in vitro and in vivo and that monocytes are the in vivo precursors of mucosal CD103(-) proi...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.01181-10

    authors: Veglia F,Sciaraffia E,Riccomi A,Pinto D,Negri DR,De Magistris MT,Vendetti S

    更新日期:2011-03-01 00:00:00

  • Cleavage of human transferrin by Porphyromonas gingivalis gingipains promotes growth and formation of hydroxyl radicals.

    abstract::Porphyromonas gingivalis, a gram-negative anaerobic bacterium associated with active lesions of chronic periodontitis, produces several proteinases which are presumably involved in host colonization, perturbation of the immune system, and tissue destruction. The aims of this study were to investigate the degradation o...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.72.8.4351-4356.2004

    authors: Goulet V,Britigan B,Nakayama K,Grenier D

    更新日期:2004-08-01 00:00:00

  • Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro.

    abstract::Clostridium difficile is recognized as the major cause of antibiotic-associated colitis. C. difficile produces two toxins, A (enterotoxin) and B (cytotoxin), that are implicated in the pathogenesis of the colitis. We examined the dose responses, time course, and synergism of these two toxins in ligated rabbit intestin...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.3.582-588.1988

    authors: Lima AA,Lyerly DM,Wilkins TD,Innes DJ,Guerrant RL

    更新日期:1988-03-01 00:00:00

  • Salmonella enterica serovars Typhimurium and Dublin can lyse macrophages by a mechanism distinct from apoptosis.

    abstract::Salmonella enterica serovars Typhimurium and Dublin lysed primary bovine alveolar macrophages and immortalized J774.2 macrophage-like cells in the absence of either the morphological changes or DNA fragmentation characteristic of apoptosis. Macrophage lysis was dependent on a subset of caspases and an intact sipB gene...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.6.3744-3747.2000

    authors: Watson PR,Gautier AV,Paulin SM,Bland AP,Jones PW,Wallis TS

    更新日期:2000-06-01 00:00:00

  • Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy.

    abstract::Nerve damage is a clinical hallmark of leprosy and a major source of patient morbidity. We investigated the possibility that human Schwann cells are susceptible to cell death through the activation of Toll-like receptor 2 (TLR2), a pattern recognition receptor of the innate immune system. TLR2 was detected on the surf...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.71.3.1427-1433.2003

    authors: Oliveira RB,Ochoa MT,Sieling PA,Rea TH,Rambukkana A,Sarno EN,Modlin RL

    更新日期:2003-03-01 00:00:00

  • Regulation of murine dendritic cell immune responses by Helicobacter felis antigen.

    abstract::Helicobacter infections are present in approximately 50% of humans, causing severe illnesses such as gastritis and malignancies. Dendritic cells (DC) are critical antigen-presenting cells which link innate and adaptive immune responses. The mechanism of dendritic cell regulation in Helicobacter-induced gastritis is po...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00289-06

    authors: Drakes ML,Czinn SJ,Blanchard TG

    更新日期:2006-08-01 00:00:00

  • Identification of a Fusobacterium nucleatum PK1594 galactose-binding adhesin which mediates coaggregation with periopathogenic bacteria and hemagglutination.

    abstract::Attachment of Fusobacterium nucleatum to various oral surfaces is mediated by several adhesins anchored on its outer surface. Monoclonal antibodies (MAbs) were prepared and used to identify the putative galactose-binding adhesin of F. nucleatum PK1594. Four unique MAbs, 8G7, 26B9, 28G11, and 29D4, were isolated on the...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.65.12.5231-5237.1997

    authors: Shaniztki B,Hurwitz D,Smorodinsky N,Ganeshkumar N,Weiss EI

    更新日期:1997-12-01 00:00:00

  • Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated.

    abstract::Intimate attachment to the host cell leading to the formation of attaching and effacing (A/E) lesions is an essential feature of enterohemorrhagic Escherichia coli (EHEC) O157:H7 pathogenesis. In a related pathogen, enteropathogenic E. coli (EPEC), this activity is dependent upon translocation of the intimin receptor,...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.67.5.2389-2398.1999

    authors: DeVinney R,Stein M,Reinscheid D,Abe A,Ruschkowski S,Finlay BB

    更新日期:1999-05-01 00:00:00

  • Chlamydia trachomatis serovar L2 induces protein tyrosine phosphorylation during uptake by HeLa cells.

    abstract::Chlamydia trachomatis L2 is an obligate intracellular microorganism with a unique biphasic life cycle. The extracellular form, the elementary body (EB), is infectious but metabolically inactive. Attachment of EBs to host cells is medicated by a heparan sulfate-like glycosaminoglycan. Following attachment, the EB is in...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.11.4900-4908.1994

    authors: Birkelund S,Johnsen H,Christiansen G

    更新日期:1994-11-01 00:00:00

  • Proteomic analysis of Vibrio cholerae in human stool.

    abstract::An effective vaccine for Vibrio cholerae is not yet available for use in the developing world, where the burden of cholera disease is highest. Characterizing the proteins that are expressed by V. cholerae in the human host environment may provide insight into the pathogenesis of cholera and assist with the development...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00585-08

    authors: LaRocque RC,Krastins B,Harris JB,Lebrun LM,Parker KC,Chase M,Ryan ET,Qadri F,Sarracino D,Calderwood SB

    更新日期:2008-09-01 00:00:00