Search results for "Conformational epitope"
showing 6 items of 6 documents
A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway
2014
CD4(+)CD25(+) regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of th…
Conformational and linear epitopes on virus-like particles of human papillomavirus type 33 identified by monoclonal antibodies to the minor capsid pr…
1995
The organization of epitopes on the minor capsid protein L2 of human papillomavirus (HPV) type 33 has been analysed using three monoclonal antibodies (MAbs) generated against a large fragment of the L2 protein (amino acids 82-259) expressed as a glutathione S-transferase fusion protein. The topology of the L2 epitopes has been investigated with respect to the structure of HPV-33 virus-like particles (VLPs). Two of the MAbs reacted with linear epitopes which were mapped to amino acids 153-160 and 163-170, respectively. These epitopes were accessible in denatured but not in native VLPs consisting of L1 and L2, suggesting an internal location. The third antibody was unable to detect denatured …
Concomitant loss of conformation and superantigenic activity of staphylococcal enterotoxin B deletion mutant proteins.
1993
The T-cell-stimulating activity of staphylococcal enterotoxin B (SEB) is an important factor in the pathogenesis of certain staphylococcal diseases. To investigate the immunologically active domains of the SEB molecule, we have produced truncated fragments of recombinant SEB by C-terminal and N-terminal deletions. The fragments were expressed as fusion proteins with protein A, including a cleavage site to remove the protein A part. Mutant proteins were tested for the ability to stimulate human resting T cells and SEB-reactive T-cell clones. Deletion of only 9 amino acids from the C terminus leads to complete loss of T-cell-stimulating activity. Removing further amino acids from the SEB mole…
Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: Characterization of the autoepitope
1995
Immunization of Balb/c mice with a homogeneously purified recombinant human La/SS-B protein resulted in activation of an autoreactive B cell secreting a novel monoclonal anti-La antibody termed La4B6. La4B6 reacted with La protein from a variety of sources including human, bovine, rat and mouse. ATP blocked the binding of La4B6 to recombinant La protein. The human epitope was identified as consisting of the amino acid sequence SKGRRFKGKGKGN, which includes the proposed ATP-binding site of the La protein. In the human and bovine La protein, the epitope exists as a continuous amino acid sequence. In rat and mouse the epitope was found to consist of the amino acid sequence SKG interrupted by a…
Characterization of a Novel Conformational GII.4 Norovirus Epitope: Implications for Norovirus-Host Interactions
2016
ABSTRACT Human noroviruses (NoVs) are the main etiological agents of acute gastroenteritis worldwide. While NoVs are highly diverse (more than 30 genotypes have been detected in humans), during the last 40 years most outbreaks and epidemics have been caused by GII.4 genotype strains, raising questions about their persistence in the population. Among other potential explanations, immune evasion is considered to be a main driver of their success. In order to study antibody recognition and evasion in detail, we analyzed a conformational epitope recognized by a monoclonal antibody (3C3G3) by phage display, site-directed mutagenesis, and surface plasmon resonance. Our results show that the predi…
Heparan sulfate proteoglycans interact exclusively with conformationally intact HPV L1 assemblies: basis for a virus-like particle ELISA.
2004
In this article, we demonstrate that interaction of human papillomavirus-like particles (HPV-VLPs) with the putative glucosaminoglycan binding receptor is strictly dependent on conformational integrity. Such conformations are present on VLPs and capsomeres but not on monomers of the major capsid protein, L1, confirming reports that capsomeres can induce virus-neutralizing antibodies. Furthermore, we show the suitability of this specific interaction for development of VLP-based enzyme-linked immunosorbent assays (ELISAs), using heparin for indirect coupling of VLPs to microtiter plates, which may add an intrinsic quality control. This avoids presentation of linear, often highly cross-reactiv…