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C J Boog

Publications and source records attributed to C J Boog.

At least 37 records · Page 2Linked to original sources
PubMed1995

Activation of virus-specific major histocompatibility complex class II-restricted CD8+ cytotoxic T cells in CD4-deficient mice.

Acute enteritic or respiratory disease is a consequence of coronavirus infection in man and rodents. Mouse hepatitis virus, stain A59 (MHV-A59) causes acute hepatitis in mice and rats and induces a response of major histocompatibility complex (MHC) class II-restricted CD4+ cytotoxic T cells, protecting mice against acute infection. In the present study we show that MHV-A59 infection of mice that lack a functional CD4 gene activates effector cells of the CD8+ phenotype. These cytotoxic T cells lyse virus-infected target cells in a MHC class II-restricted fashion. The results indicate that CD8+ T cells have the potential to utilize MHC class II as restriction element, illustrating that the immune system can effectively deal with evading microorganisms, such as viruses which down-regulate MHC class I.

Animals↗
PubMed1995

Leishmania infantum-specific T cell lines derived from asymptomatic dogs that lyse infected macrophages in a major histocompatibility complex-restricted manner.

Protective immunity to leishmaniasis has been demonstrated in murine models to be mediated by T cells and the cytokines they produce. We have previously shown that resistance to experimental Leishmania infantum infection in the dog, a natural host and reservoir of the parasite, is associated with the proliferation of peripheral blood mononuclear cells (PBMC) to parasite antigen and to the production of interleukin-2 and tumour necrosis factor. In this study we show that PBMC from asymptomatic experimentally infected dogs produce interferon-gamma upon parasite antigen-specific stimulation, whereas lymphocytes from symptomatic dogs do not. In addition, we report for the first time the lysis of L. infantum-infected macrophages by PBMC from asymptomatic dogs and by parasite-specific T cell lines derived from these animals. These T cell lines were generated by restimulation in vitro with parasite soluble antigen and irradiated autologous PBMC as antigen-presenting cells. We show that lysis of infected macrophages by T cell lines is major histocompatibility complex restricted. Characterization of parasite-specific cytotoxic T cell lines revealed that the responding cells are CD8+. However, for some animals, CD4+ T cells that lyse infected macrophages were also found. In contrast to asymptomatic dogs, lymphocytes from symptomatic dogs failed to proliferate and produce interferon-gamma after Leishmania antigen stimulation in vitro and were not capable of lysing infected macrophages. These results suggest that both the production of interferon-gamma and the destruction of the parasitized host cells by Leishmania-specific T cells play an important role in resistance to visceral leishmaniasis.

Animals↗
PubMed1995

Vaccination against feline immunodeficiency virus using fixed infected cells.

Crandell feline kidney cells and feline thymocytes, either feline immunodeficiency virus (FIV) infected or uninfected, were fixed with paraformaldehyde and used to vaccinate cats. The cells were mixed with a 30:70 water/mineral oil emulsion containing 250 micrograms ml-1 N-acetyl-D-glucosaminyl-beta-(1-4)-N-acetyl-muramyl-L-alanyl-D-isoglutam ine. Eighteen specific pathogen-free cats were vaccinated three times with 3-week intervals and challenged 21 days after the final boost with a low dose of the homologous FIV-UT113 strain. Eight out of ten cats that had received FIV-infected cell vaccines developed significant anti-FIV antibody titres to the envelope and core antigens. Neutralizing antibodies were detectable at the moment of challenge in the sera of these animals. Within 5 weeks after challenge 15 out of 18 cats became viraemic. Three animals, two that had been vaccinated with FIV-infected thymocytes and did not develop antibody, and one that had received an uninfected thymocyte preparation, remained uninfected for 6 months. Upon rechallenge of the three animals, two again resisted infection; these cats had been immunized with the infected and the uninfected thymocyte preparations, respectively.

Animals↗
PubMed1995

Differential activation of mouse hepatitis virus-specific CD4+ cytotoxic T cells is defined by peptide length.

In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4+ cytotoxic T lymphocyte (CTL) clones HS1 and B6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4+ clones respond to the promiscuous peptide fragment S-329-343 of the glycoprotein S of MHV-A59. The results indicate that the core peptides of both clones overlap but are not identical. The core region of the HS1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises the amino acid residues S-334-342. The peptide fragment S-329-343 activates all T-cell effector functions, including proliferation, cytokine secretion and cytolysis. However, in the present study we show that T-cell activation is not an all-or-none phenomenon, in which T-cell stimulation leads to activation of all T-cell effector functions. It appears that changes in the length of a peptide ligand can differentially activate the cytolytic machinery from proliferation and cytokine secretion. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytokine profile of polarized T-helper type-1 (Th1) clones into a Th2-type pattern.

Amino Acid Sequence↗
PubMed1995

Activated rat T cells synthesize and express functional major histocompatibility class II antigens.

In the present report, we studied the presence and functional significance of major histocompatibility complex (MHC) class II antigen on rat T cells. Most rat T-cell lines cultured in vitro were found to be MHC class II+. Also, these T-cell lines were shown to synthesize MHC class II molecules. Immunohistochemical and flow cytometric double stainings for T-cell receptor (TCR) and MHC class II showed that in vivo as well a large proportion of T cells was MHC class II+. The immunohistochemical staining of spleen sections enabled us to characterize the MHC class II+ and MHC class II- T cells. It was shown that resting T cells in vivo were MHC class II-. In contrast, activated T cells, as determined by their localization in the marginal zone of the spleen, proved to be MHC class II+. Finally, T-cell clones were found to be able to present peptidic antigens, but could only poorly present more complex exogenous antigens, probably due to inefficient uptake of such antigens. These features would endow activated rat T cells with the capacity to present cell-specific self-proteins, such as TCR, to regulatory CD4+ MHC class II-restricted T cells, as was described by our group elsewhere.

Animals↗
PubMed1995

Predominance of MHC class II-restricted CD4+ cytotoxic T cells against mouse hepatitis virus A59.

Coronavirus-induced acute hepatitis is a complex event and the role of different components of the immune system with regard to defined viral proteins and the course of the infection is not yet clear. We have analysed the cytotoxic T-lymphocyte (CTL) response in mouse hepatitis virus (MHV-A59) infection. Surprisingly, we detected only a very clear virus-specific major histocompatibility complex (MHC) class II-restricted cytotoxicity in mice infected with MHV-A59. We found no evidence of activation of the classical CD8+ MHC class I-restricted CTL. The virus-specific CD4+ CTL derived from two different mouse strains having different MHC haplotypes recognized the same immunodominant epitope. This epitope, comprising the amino acid residues 329-343 of the viral S-glycoprotein, was recognized both at the polyclonal level and by virus-specific CTL clones. Transfer studies using a MHV-A59-specific CD4+ CTL clone showed significant protection against a lethal challenge with MHV-A59, implicating that these CD4+ CTL play a pivotal role in the protection against MHV-A59 infections.

Animals↗
PubMed1994

CDR1 T-cell receptor beta-chain peptide induces major histocompatibility complex class II-restricted T-T cell interactions.

T-T cell interactions have been proposed in postulated network theories of immunoregulation and autoimmunity. Despite previous reports of protection induced by T-cell receptor (TcR)-derived peptides in experimental autoimmunity, no evidence for T-T cell interactions by direct recognition of processed TcRs on native T cells was obtained. Here we report that immunization of rats with overlapping sets of peptides of the TcR alpha or beta chain allowed us to detect immunogenic TcR peptides. Remarkably enough, these TcR peptides appeared to cluster within the hypervariable complementarity-determining regions of the TcR. Immunization of rats with these TcR peptides induced CD4+ TcR peptide-specific T cells, which recognized both rDNA TcR proteins and the original, arthritogenic T cell in a major histocompatibility complex class II-restricted way. These findings indicate that activated T cells can process and present their own TcR in the context of major histocompatibility complex class II molecules and, furthermore, that such peptides can be recognized by TcR variable gene-specific T cells.

Amino Acid Sequence↗
PubMed1994

Inhibition of experimental autoimmune encephalomyelitis by MHC class II binding competitor peptides depends on the relative MHC binding affinity of the disease-inducing peptide.

Blocking of the Ag presentation function of MHC molecules by competitor peptides has been proposed as a potential immunotherapy for MHC-associated autoimmune diseases. Despite the fact that successful inhibition of experimental autoimmune encephalomyelitis (EAE) by coimmunization with competitor peptides had been achieved, it remained questionable whether the in vivo activity of such peptides was solely the result of MHC blockade. In the peptide MBP72-85-induced EAE model in Lewis rats, we designed a single amino acid-substituted analogue of MBP72-85 with a superior MHC binding capacity, and with the capacity to activate encephalitogenic MBP72-85-specific T cells. Subsequently, two well-defined competitor peptides, one EAE related and one non-EAE related, were studied for their respective efficacies to inhibit the in vitro proliferation of an encephalitogenic T cell clone induced by the original MBP72-85 or the superior MHC binding analogue peptide. It appeared that the response to MBP72-85 was inhibited very efficiently by both competitor peptides, whereas the response to the superior MHC binding analogue peptide was not. Co-immunization of either the related or non-related competitor peptide together with MBP72-85 inhibited EAE induction in a concentration-dependent manner. In such protected rats, polyclonal T cell responses against MBP72-85 were dramatically decreased. However, EAE induced by the stronger MHC binding MBP72-85 analogue could not be inhibited by either of the competitor peptides. Moreover, in these rats, T cell priming for both MBP72-85 and the MBP72-85 analogue was not inhibited. These results show that competition for MHC binding in vivo could lead to inhibition of EAE induction.

Amino Acid Sequence↗
PubMed1994

Inhibition of entire myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats by major histocompatibility complex class II-binding competitor peptides.

Previous studies have shown that major histocompatibility complex (MHC) blockade by competitor peptides with high MHC class II binding affinity can prevent peptide-induced experimental autoimmune encephalomyelitis (EAE). However, none of these studies addressed the question whether this approach could also be used to prevent EAE induced with a multivalent antigen. In this report we show the effect of competitor peptides co-immunized during EAE induction with entire guinea pig myelin basic protein (MBP) in Lewis rats. As MHC class II binding competitor peptides we used one nonimmunogenic disease-nonrelated peptide, and two immunogenic peptides, one EAE-related and one non-EAE-related. The respective efficacy of these three competitor peptides to inhibit MBP-induced proliferation of an encephalitogenic T cell line in vitro correlated with their respective MHC binding affinity. Co-immunization of the competitor peptides during disease induction with entire MBP resulted in a competitor concentration-dependent inhibition of clinical signs of EAE. These results demonstrate that, although polyclonal T cell responses to MBP were not completely inhibited, co-administration of immunogenic or nonimmunogenic either EAE-related or non-EAE-related MHC class II binding competitor peptides can inhibit the development of EAE induced with entire MBP.

Animals↗
PubMed1994

Differential rat T cell recognition of cathepsin D-released fragments of mycobacterial 65 kDa heat-shock protein after immunization with either the recombinant protein or whole mycobacteria.

T cells specific for the mycobacterial 65 kDa heat-shock protein (hsp65) play a pivotal role in the development of adjuvant arthritis (AA) in Lewis rats. Upon adoptive transfer, CD4+ T cells recognizing a particular hsp65 epitope trigger the onset of disease. Activation of hsp65-reactive T cells can be achieved by immunization with heat-killed mycobacteria in mineral oil--complete Freund's adjuvant (CFA)--or with purified recombinant hsp65. Arthritis, however, will only develop after immunization with CFA. In fact, preimmunization with hsp65 protects against any subsequent attempt to induce AA. In this study, we examined polyclonal lymph node cell responses in Lewis rats, immunized with either CFA or purified recombinant hsp65 in incomplete Freund's adjuvant, to a set of hsp65 fragments generated by a mild digestion with cathepsin D. Proliferative responses to several hsp65 fragments varied with the type of antigen used for immunization. A cathepsin D-released fragment, identified as residues 376-408, preferentially triggered proliferation of rat T cells after hsp65 immunization. Preimmunization of Lewis rats with this peptide delayed the onset and reduced the severity of AA. Preimmunization with another fragment which was preferentially recognized after CFA immunization, representing residues 40-60, did not have such a protective effect. Our findings suggest the presence of mycobacterial hsp65 determinants that selectively trigger AA-regulating T cells and illustrate that cathepsin D may be used as an experimental tool to generate such determinants.

Amino Acid Sequence↗
PubMed1994

Identification of an H-2 Kb-presented Moloney murine leukemia virus cytotoxic T-lymphocyte epitope that displays enhanced recognition in H-2 Db mutant bm13 mice.

Upon infection with the Moloney murine sarcoma virus-murine leukemia virus (MuLV) complex, H-2b C57BL/6 (B6) mice respond with a class I Db-restricted cytotoxic T-lymphocyte (CTL) response, which protects against virus-induced tumorigenesis. In the B6-derived Db mutant B6.CH-2bm13 (bm13) strain, part of the class I Db antigen-presenting groove is shaped by a class I Kb-encoded sequence. Like B6 mice, bm13 mice reject Moloney virus-induced tumors, but the protective CTL response is Kb restricted. In this study we show enhanced levels of Moloney MuLV-specific CTLp with a restriction for Kb in bm13 mice. Through the use of CTL clones from Moloney virus-immunized bm13 mice, the class I Kb-presented CTL epitope was identified. The epitope is located in the Moloney virus gp70 envelope protein region (Moloney envelope, amino acids 189 to 196 [Mol env (189-196)]), SSWDFITV and has the Kb allele-specific binding motif. The Dbm13 molecule does not present the env(189 to 196) epitope to Kb-restricted bm13 CTL. In B6 mice, Mol env(189-196)-specific CTL could be induced by peptide vaccination. B6 mice thus have CTL precursors specific for this epitope but at considerably lower levels than do bm13 mice. We hypothesize that additional positive selection of Kb-restricted CTL on the Dbm13 molecule in bm13 mice explains this difference in precursor frequencies. We examined related strains of MuLV for the presence of Mol env(189-196) sequence equivalents. Rauscher, Friend, and AKV MuLV-encoded Mol env(189-196) epitope equivalents were properly recognized in cytotoxicity assays, both as synthetic and as endogenously expressed (Rauscher MuLV) peptides. In contrast, the mink cell focus-forming virus MuLV-encoded epitope equivalent, lacking a Kb anchor residue, was not presented for CTL recognition and hence can be excluded as an important CTL epitope for mink cell focus-forming viruses.

Amino Acid Sequence↗
PubMed1993

A peptide variant of an arthritis-related T cell epitope induces T cells that recognize this epitope as a synthetic peptide but not in its naturally processed form.

The immune system has the potential to utilize a diverse T cell repertoire for the recognition of Ag in the context of MHC molecules. Here we describe the analysis of two rat T cell clones, both of which recognize a synthetic peptide comprised of the arthritis-associated 180-188 amino acid sequence of the mycobacterial 65-kDa heatshock protein (hsp65 180-188), but which differ in the recognition of the naturally processed hsp65. The arthritogenic T cell clone A2b, generated by immunization with whole Mycobacterium tuberculosis, recognized the hsp65 180-188 synthetic peptide as well as the processed hsp65, whereas T cell clone ATL11, generated after immunization with a single amino acid substituted peptide analog of hsp65 180-188, recognized peptide hsp65 180-188 but not the processed hsp65. For both T cell clones the minimal stimulatory sequence was hsp65 180-186. However, within this minimal stimulatory sequence marked differences between the clones were found with regard to peptide residues interacting with the TCR. Furthermore, addition of extra residues at the N terminus of the hsp65 180-186 sequence abrogated the recognition by clone ATL11, but not by A2b. These findings demonstrate that, upon in vivo immunization with a synthetic peptide comprised of a single amino acid variant of a T cell epitope, T cells can be triggered that recognize a peptide comprised of the original epitope sequence, but that do not recognize this epitope in its naturally processed protein fragment. The possibility of triggering such T cells by immunization with synthetic peptides, may well have consequences for the design of peptide vaccines or peptide immunomodulatory agents.

Amino Acid Sequence↗
PubMed1992

Disease inhibition by major histocompatibility complex binding peptide analogues of disease-associated epitopes: more than blocking alone.

Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that antigen-specific regulatory mechanisms were involved in synergy with MHC competition. The integration of both qualities into a single "competitor-modulator" analogue peptide may lead to the development of novel, more effective, disease-specific immunomodulatory peptides.

Alanine↗