A novel method for detecting antigen-specific human regulatory T cells
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Monoclonal antibody 2F5 recognizing the ELDKWA epitope on HIV-1 gp41 has a significant neutralization potency against 90% of the investigated viruses of African, Asian, American, and European strains, but the antibody responses to the epitope 2F5 in HIV-1-infected individuals were very low. We attempted to induce high levels of epitope-specific antibodies to ELDKWA and its three mutated epitopes by candidate epitope vaccines. The four candidate epitope vaccines all induced strong antibody responses at dilutions from about 1:6,400 to 1:25,600. We tested the cross-reactions between these antisera and four epitope peptides. The ELDKWA-specific antisera showed strong cross-reactivity with three neutralizing-resistant mutated epitopes which contain changes in the D or K positions of the epitope sequence. Virus variants containing these changes could escape neutralization by monoclonal antibody 2F5. In immunoblotting analysis, the ELDKWA, ELDEWA, and ELEKWA epitope specific antibodies all recognized rsgp41 which confirms that the antibodies against both mutated epitopes, ELDEWA and ELEKWA, could cross-react with the native epitope on rsgp41. Although it is not clear whether the polyclonal antibodies induced by the ELDKWA epitope vaccine could neutralize the mutated viruses containing these mutated epitopes, it is conceivable that epitope vaccines based on mutated epitopes could induce strong antibody responses with predefined epitope specificity to neutralize mutated viruse containing the mutated epitope. An epitope vaccine, using different epitopes including mutated epitopes, could provide a new concept for developing a new vaccine against HIV-1.
Linear epitope
Polyclonal antibodies
Epitope mapping
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The humoral immune system response is based on the interaction between antibodies and antigens for the clearance of pathogens and foreign molecules. The interaction between these proteins occurs at specific positions known as antigenic determinants or B-cell epitopes. The experimental identification of epitopes is costly and time consuming. Therefore the use of in silico methods, to help discover new epitopes, is an appealing alternative due the importance of biomedical applications such as vaccine design, disease diagnostic, anti-venoms and immune-therapeutics. However, the performance of predictions is not optimal been around 70% of accuracy. Further research could increase our understanding of the biochemical and structural properties that characterize a B-cell epitope.We investigated the possibility of linear epitopes from the same protein family to share common properties. This hypothesis led us to analyze physico-chemical (PCP) and predicted secondary structure (PSS) features of a curated dataset of epitope sequences available in the literature belonging to two different groups of antigens (metalloproteinases and neurotoxins). We discovered statistically significant parameters with data mining techniques which allow us to distinguish neurotoxin from metalloproteinase and these two from random sequences. After a five cross fold validation we found that PCP based models obtained area under the curve values (AUC) and accuracy above 0.9 for regression, decision tree and support vector machine.We demonstrated that antigen's family can be inferred from properties within a single group of linear epitopes (metalloproteinases or neurotoxins). Also we discovered the characteristics that represent these two epitope groups including their similarities and differences with random peptides and their respective amino acid sequence. These findings open new perspectives to improve epitope prediction by considering the specific antigen's protein family. We expect that these findings will help to improve current computational mapping methods based on physico-chemical due it's potential application during epitope discovery.
Linear epitope
Reverse vaccinology
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Epitope-vaccine is a newly developing vaccine which has many advantages comparied with to the traditional vaccine.The key step for designing epitope-vaccine is to screen epitopes.The epitope-screening methods include protein degration,peptide-probing scanning,epitope prediction by computer,et al.Usually,the epitope-vaccine needs combine some carriers to display immunologic activity,for example,lipid carriers,protein carriers,and adjuvant.In addition,researchers also use tandem repeat epitopes,conformational multiple antigen peptide(MAP) and epitope modifying to strengthen the immunological efficacity.The epitope-vaccine mainly contains viral epitope-vaccine,bacterial epitope-vaccine and epitope-vaccine for parasites.Although the researches on epitope-vaccine develop fast,some problems and challenges need to resolve impendingly.
Peptide vaccine
Epitope mapping
Linear epitope
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A single antigen (SA) Luminex beads assay was used to detect antibody specificities of allosera and monoclonal antibodies. Potential antibody epitopes were mapped by comparing the protein sequence differences of a group of HLA alleles that are either recognized or unrecognized by tested samples. A total of 61 epitopes, including 43 one amino acid (AA) epitopes, 11 two AA epitopes, and 7 epitopes with more than two residues involved, were identified. Among 38 residues constituting DR epitopes, 26 of them located in beta1 domain and 12 located in beta2 domain. Only 42% of beta1 domain epitopes are surface residues, while 83% of beta2 domain epitopes are on an antigen surface. These findings imply that some polymorphic AA residues, especially those on beta1 domain, may be indirectly involved in antibody-antigen interactions. In conclusion, sequence comparison following SA beads tests provides an ideal approach for epitope identification of HLA-specific antibody. Certainly, these identified potential epitopes need to be further proved or disproved by other approaches, such as absorption/elution from SA beads or cell lines, each of which contains unique epitope pattern.
Linear epitope
Epitope mapping
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In order to obtain further information on the biological role of the HER2/neu oncoprotein, 7 new monoclonal antibodies (MAbs) were produced against the pl85HER2 extracellular domain. These MAbs, together with two others previously produced, were used to investigate the pl85HER2 expression in breast carcinomas and compare the recognized antigenic determinants. The 7 reagents (MGR4,5,6,7,8,9 and 10), were shown to define five distinct epitopes. Three of these MAbs (MGR5,7,10), as well as one previously produced (MGR2), recognize the same epitope (Epitope-1) which seems, therefore, to be highly immunogenic for the murine immune system. Epitope-2 recognized by the MGR4 MAb, appears to be closely related to epitope-1 due to a cross inhibition between MGR4 and MGR10, but not MGR2. Epitope-2 is the only one of the 5 also present on the product of the neu oncogene, the rat analogue of the human HER2/neu gene. None of the reagents against epitope-1 and epitope-2 were found to mediate receptor internalization, whereas MGR6 as well as a previously produced MAb (MGR3), both of which define epitope-3 and MGR8 which defines epitope-4, were found to do so. Epitope-4 like the neu-specific peptide recognized by the reference c-neu Ab3 MAb, was detectable on all p185HER2 positive breast cancer, independently from the quantitative content of the oncoprotein, at variance with the other 4 epitopes whose availability on p185HER2 for the relevant MAbs varied with the degree of overexpression. Epitope-5, recognized by the MGR9 MAb, on the contrary to the other epitopes, was prevalently localized at the basal membrane level of the tumor nodule.
Linear epitope
HER2/neu
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Linear epitope
Epitope mapping
Immunofluorescence
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Linear epitope
Keyhole limpet hemocyanin
Epitope mapping
Antigenicity
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Linear epitope
Bovine herpesvirus 1
Epitope mapping
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Background As an essential step of adaptive immune response, the recognition between antigen and antibody triggers a series of self-protection mechanisms. Therefore, the prediction of antibody-binding sites (B-cell epitope) for protein antigens is an important field in immunology research. The performance of current prediction methods is far from satisfying, especially for conformational epitope prediction. Here a multi-perspective analysis was carried on with a comprehensive B-cell conformational epitope dataset, which contains 161 immunoglobulin complex structures collected from PDB, corresponding to 166 unique computationally defined epitopes. These conformational epitopes were described with parameters from different perspectives, including characteristics of epitope itself, comparison to non-epitope surface areas, and interaction pattern with antibody. Results According to the analysis results, B-cell conformational epitopes were relatively constant both in the number of composing residues and the accessible surface area. Though composed of spatially clustering residues, there were sequentially linear segments exist in these epitopes. Besides, statistical differences were found between epitope and non-epitope surface residues with parameters in residual and structural levels. Compared to non-epitope surface residues, epitope ones were more accessible. Amino acid enrichment and preference for specific types of residue-pair set on epitope areas have also been observed. Several amino acid properties from AAindex have been proven to distinguish epitope residues from non-epitope surface ones. Additionally, epitope residues tended to be less conservative under the environmental pressure. Measured by topological parameters, epitope residues were surrounded with fewer residues but in a more compact way. The occurrences of residue-pair sets between epitope and paratope also showed some patterns. Conclusions Results indicate that, certain rules do exist in conformational epitopes in terms of size and sequential continuity. Statistical differences have been found between epitope and non-epitope surface residues in residual and structural levels. Such differences indicate the existence of distinctiveness for conformation epitopes. On the other hand, there was no accordant estimation for higher or lower values derived from any parameter for epitope residues compared with non-epitope surface residues. This observation further confirms the complicacy of characteristics for conformational epitope. Under such circumstance, it will be a more effective and accurate approach to combine several parameters to predict the conformation epitope. Finding conformational epitopes and analysing their properties is an important step to identify internal formation mechanism of conformational epitopes and this study will help future development of new prediction tools.
Linear epitope
Conformational epitope
Epitope mapping
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