Biomedical subjects

M Wauben

Publications and source records attributed to M Wauben.

6 recordsLinked to original sources

PubMed2000

Artificial antigen-presenting cells as a tool to exploit the immune 'synapse'.

Recent progress in molecular medicine has provided important tools to identify antigen-specific T cells. In most cases, the approach is based on oligomeric combinations of recombinant major histocompatibility complex-peptide complexes fixed to various rigid supports available for binding by the T-cell receptor. These tools have greatly increased our insight into mechanisms of immune responses mediated by CD8+ T cells. Examples of the diverse fields of application for this technology include immunization, viral infections and oral tolerance induction.

Antigen Presentation↗

PubMed1998

Nasal administration of arthritis-related T cell epitopes of heat shock protein 60 as a promising way for immunotherapy in chronic arthritis.

Adjuvant Arthritis (AA) can be induced in Lewis rats by immunisation with mycobacterial antigens. The disease can be passively transferred with T cell clone A2b, which recognises the 180-188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) and which crossreacts with crude cartilage proteoglycans. We succeeded to induce peripheral tolerance to this AA-associated T cell epitope following nasal administration of a peptide containing this epitope (mycobacterial hsp60 176-190). In rats treated nasally with 176-190 and immunised with mycobacterial hsp60, proliferative responses to 176-190 were reduced. AA was inhibited nasally with 176-190 treated rats and not in rats nasally treated with a control mycobacterial hsp60 peptide (211-225). Moreover, nasal 176-190 led to similar arthritis protective effects in a non-microbially induced experimental arthritis (avridine induced arthritis). In a subsequent study we tried to prevent and to treat AA through nasal administration of mycobacterial hsp60 peptide 180-188 and a peptide analogue of 180-188, 180-188(L183->A) (Alanine 183), which has been shown to have an increased MHC-binding affinity for rat RT1 Bl and an increased capacity to inhibit the proliferative A2b response in vitro. We found that nasal administration of 180-188 had a moderate arthritis suppressive effect in AA, whereas its analogue peptide Alanine 183, had a strong suppressive effect. This strong arthritis suppressive effect was only partly due to the higher MHC-binding affinity for rat RT1 Bl. Furthermore, it was possible to passively transfer nasal Alanine 183 induced disease protection. The present findings may in our view offer novel prospects for immunotherapy through nasal administration of (analogue) peptides, with a mimicry relationship with joint specific cartilage proteoglycan epitopes.

Administration, Intranasal↗

PubMed1994

Immunogenicity of a mycobacterial T-cell epitope expressed in outer membrane protein PhoE of Escherichia coli.

The outer membrane protein PhoE of Escherichia coli can be used for the expression of foreign antigenic determinants. Previously, a T-cell epitope of the 65 kDa heat shock protein (hsp65) of Mycobacterium tuberculosis, comprising amino acids 180 to 188, was expressed in PhoE. The hybrid protein induced proliferation of epitope-specific T-cell clones in vitro. In this report, the potential of the hybrid protein to induce an in vivo T-cell response against the 180-188 T-cell epitope was assessed. Popliteal lymph node cells, isolated from rats immunized with PhoE containing the hsp65 epitope, showed high proliferative responses to a synthetic peptide consisting of amino acids 180 to 188 of hsp65, indicating that the epitope is immunogenic in the PhoE-associated conformation.

Animals↗

PubMed1994

Influence of amino acids of a carrier protein flanking an inserted T cell determinant on T cell stimulation.

CD4+ helper T cells recognize antigen in association with MHC class II molecules. To investigate the role of the context of a minimal T cell epitope on presentation and recognition in association with MHC class II molecules, an epitope of the 65 kDa heat shock protein of Mycobacterium tuberculosis was inserted at four different sites in the outer membrane protein PhoE of Escherichia coli. Only some of the constructs could stimulate the epitope-specific T cell clone A2b in vitro. One non-stimulatory construct could be made stimulatory by denaturation, suggesting that the protein conformation prevents correct presentation of the epitope. Other non-stimulatory constructs did not become stimulatory with denaturation. One of these constructs could be made stimulatory by substitution of either one of the two amino acids directly preceding the minimal epitope in the recombinant protein. In synthetic peptides the presence of these upstream residues did not interfere with T cell recognition, suggesting that these residues influence processing of the recombinant protein. Flanking amino acids also influenced induction of a T cell response against the inserted epitope in vivo. These results demonstrate that insertion of minimal T cell epitopes in carrier proteins for the design of vaccines might fail because of the inhibiting effects of flanking residues.

Amino Acid Sequence↗

PubMed1993

Inhibition of T-cell proliferation by rat synoviocytes.

Antigen presentation by synoviocytes to arthritis-related T-cell clones was studied in Lewis rats. Freshly isolated synoviocytes may be able to take up and process mycobacterial antigens but they seem inefficient as antigen presenting cells. Furthermore, synovial cells inhibited the specific proliferative responses of T lymphocytes by a mechanism which apparently was not antigen-specific or mediated by secreted cytokines. Synovial cells isolated from rats at the period of developing adjuvant arthritis showed a lower inhibitory capacity associated with a lower degree of antigen clearance. These results suggest that synoviocytes might inhibit T-cell responses in normal joints and that this negative control diminishes following arthritis induction.

Animals↗

PubMed1988

Genetic manipulation of major P-fimbrial subunits and consequences for formation of fimbriae.

The influence of genetic manipulation of the structural genes coding for major P-fimbrial subunits on the formation of fimbriae in Escherichia coli was studied. Deletion of two regions that code for hypervariable parts of the P fimbrillin resulted in strong reduction or total absence of fimbria production. Replacement of deleted amino acids by other amino acid residues restored the formation of fimbriae. The hypervariable regions may be important for biogenesis of fimbriae by imposing correct spacing between conserved regions of the protein. The potential for substituting amino acids in the P-fimbrial subunit opens interesting possibilities for use of fimbriae as carriers of foreign antigenic determinants. An antigenic determinant of foot-and-mouth disease virus (FMDV) was incorporated in the F11 fimbrial subunit. Hybrid fimbriae, recognized by an FMDV-specific neutralizing monoclonal antibody directed against FMDV, were formed.

Amino Acid Sequence↗