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Biomedical subjects

R Van Der Zee

Publications and source records attributed to R Van Der Zee.

6 recordsLinked to original sources
PubMed2004

Changes in the reproductive system of male mice immunized with a GnRH-analogue conjugated to mycobacterial hsp70.

Immunosterilization is an attractive alternative to surgical castration. Gonadotropin-releasing hormone (GnRH) controls the production of the gonadotropins thereby having an orchestrating effect on the reproductive hormone cascade and spermatogenesis. Induction of neutralizing antibody can abrogate the effect of the hormone. Current GnRH-based vaccines often require strong adjuvants and/or multiple injections of the vaccines to overcome variability in the response. Heat shock proteins (hsp) have been used as carrier molecules because of their powerful intrinsic ability to enhance an immune response to associated antigens. A GnRH-analogue, GnRH-d6-Lys, was conjugated to recombinant Mycobacterium tuberculosis hsp70. Male BALB/c mice were immunized i.p. with GnRH-hsp70 in the mild adjuvant Ribi or in incomplete Freund's adjuvant (IFA). The initial immunizations were done on pre-pubertal 3-week-old mice, with boosts at 5 and 8 weeks of age. The mice were killed at 10 weeks of age and GnRH-specific antibodies and serum testosterone levels measured. All the immunized mice mounted GnRH-specific antibody responses, with no difference in the mice immunized with GnRH-hsp70/Ribi or with GnRH-hsp70/IFA. There was substantial atrophy of the urogenital complex and significantly (P < 0.0005) reduced levels of testosterone-dependent testicular relaxin-like factor mRNA expression. Mice immunized with GnRH-hsp70/Ribi showed substantially reduced (P < 0.001) serum testosterone levels. These results indicate that hsp70 may serve as a particularly advantageous carrier for GnRH-based vaccines.

Adjuvants, Immunologic↗
PubMed2001

Antineutrophil cytoplasmic antibodies to proteinase 3 in Wegener's granulomatosis: epitope analysis using synthetic peptides.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) to proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity nor to functional effects of these antibodies in vitro, suggesting differences in epitope specificity. To define relevant epitopes for PR3-ANCA, sera of WG patients were analyzed on their reactivity to linear peptides of PR3. METHODS: Fifty linear peptides of 15 amino acids in length with an overlap of 10 aa spanning the entire PR3 sequence were synthesized. Sera of 27 WG patients with active disease and 27 age- and sex-matched healthy controls, eight anti-PR3 monoclonal antibodies (mAbs), and a rabbit anti-PR3 serum were tested by enzyme-linked immunosorbent assay for reactivity to PR3 peptides. RESULTS: Rabbit anti-PR3 serum recognized three distinct peptide areas, whereas none of the anti-PR3 mAbs bound PR3 peptides. Sera of both WG patients and healthy controls recognized a restricted number of PR3 peptides. Four of these peptide areas were recognized significantly more strongly by WG sera than by control sera. Sera drawn at the initial presentation of WG mainly recognized these peptides. Two of the recognized peptide areas were located near the active center of PR3. CONCLUSION: A restricted number of epitope areas of PR3 are recognized both by WG patient sera and control sera. Four peptide areas were bound stronger by sera of WG patients at initial presentation than by healthy controls.

Adult↗
PubMed1996

(Altered) self peptides and the regulation of self reactivity in the peripheral T cell pool.

Tolerance for self has appeared incomplete for many self antigens. We have obtained experimental evidence that both for self heat shock proteins and T cell receptor V-gene products, reactive T cells are part of the normal immune repertoire. Furthermore, it has become apparent that stimulation of T cell responsiveness to these antigens, by using peptide immunisation or by transfer of activated T cells, raises resistance to experimentally induced autoimmune arthritis. In addition, available evidence has suggested that these reactivities may be functional during natural processes of disease remission. The observations with regard to heat-shock proteins have indicated that mechanism leading to disease resistance are most efficiently triggered by exposing the immune system to non-self antigens such as bacterial hsp's, which are similar to, but not identical to, self. Experimental evidence has been obtained, that conserved bacterial hsp peptides, may trigger self hsp reactive T cells, with disease suppressive regulatory potential. It is possible that such self hsp reactive T cells, being expanded by recognising bacterial peptides as full agonists, do, in fact, perceive the self epitopes as partial agonists, and therefore have the possibility of displaying downregulatory activity at the site of inflammation. Experiments with peptide analogs of self epitopes, being variants of disease critical T cell epitopes, have indeed suggested that also their activity in modulating disease may comply with the principles of dominant immunological tolerance.

Amino Acid Sequence↗
PubMed1993

In vivo response of murine gamma delta T cells to a heat shock protein-derived peptide.

Recent results suggested that a large subset of heat shock protein HSP-60 reactive peripheral lymphoid gamma delta T cells preexists in normal adult mice, all members of which respond to a single segment of this common HSP. However, the experimental evidence supporting this idea involved in vitro peptide responses of gamma delta T-cell hybridomas generated from unprimed spleen cells. Here, we report an attempt to elicit a gamma delta T-cell response in vivo by stimulation of adult C57BL/10 mice with HSP-60 or an HSP-60-derived peptide fragment comprising amino acids 180-196 of mycobacterial HSP-60. Whereas no gamma delta T-cell response was detectable in mice injected with the intact protein, stimulation with the peptide altered the reactive gamma delta T-cell population in vivo. These changes were detected among hybridomas generated with cells restimulated in vitro and included a large increase in hybridizable gamma delta T cells, a nearly maximal increase in the relative frequency of HSP-60-reactive cells, and structural changes in expressed T-cell receptors of HSP-60-reactive cells. Interestingly, we failed to elicit a detectable alpha beta T-cell response to the particular peptide stimulatory for gamma delta T cells, although at least three other HSP-60 epitopes were recognized. Our data show that normal gamma delta T cells can respond in vivo to small peptide antigens. The gamma delta T-cell response to the HSP-60-derived peptide studied here is apparently independent of antigen-specific alpha beta T-cell reactivity.

Animals↗
PubMedDate not supplied

Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.

Oral administration of E. coli extract OM-89 is used in treating RA. It has been shown that immune reactivity to heat-shock proteins (hsp) is involved in immunomodulation of arthritis. We evaluated the postulated presence and immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were found in rats immunized with OM-89. And conversely, immunization with hsp antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a major immunogenic constituent of OM-89. Parenteral immunization with OM-89 reduces resistance to adjuvant arthritis (AA), whereas oral administration protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA our findings suggest peripheral tolerance induced by hsp-specific regulatory T cells as a mode of action for OM-89 as an arthritis suppressive oral drug.

Animals↗