Cell Epitopes Of Proteins Research Articles

Prediction of B cell epitopes in proteins using a novel sequence similarity-based method

Prediction of B cell epitopes that can replace the antigen for antibody production and detection is of great interest for research and the biotech industry. Here, we developed a novel BLAST-based method to predict linear B cell epitopes. To that end, we generated a BLAST-formatted database upon a dataset of 62,730 known linear B cell epitope sequences and considered as a B cell epitope any peptide sequence producing ungapped BLAST hits to this database with identity ≥ 80% and length ≥ 8. We examined B cell epitope predictions by this method in tenfold cross-validations in which we considered various types of non-B cell epitopes, including 62,730 peptide sequences with verified negative B cell assays. As a result, we obtained values of accuracy, specificity and sensitivity of 72.54 ± 0.27%, 81.59 ± 0.37% and 63.49 ± 0.43%, respectively. In an independent dataset incorporating 503 B cell epitopes, this method reached accuracy, specificity and sensitivity of 74.85%, 99.20% and 50.50%, respectively, outperforming state-of-the-art methods to predict linear B cell epitopes. We implemented this BLAST-based approach to predict B cell epitopes at http://imath.med.ucm.es/bepiblast.

Bioinformatics analysis of candidate proteins Omp2b, P39 and BLS for Brucella multivalent epitope vaccines

This study focuses on analyzing the physicochemical properties, structural characteristics and dominant epitopes of Brucella outer membrane protein 2b (Omp2b), periplasmic binding protein (P39) and Brucella lumazine synthase (BLS) proteins by bioinformatics methods, and to provide a theoretical basis for constructing multi-epitope vaccines. The amino acid sequences of three kinds of proteins were obtained from the UniProt database. The highest frequency alleles in northern China were obtained from the AlleleFrequencies database. Analysis of the physicochemical properties of the proteins by ProtParam online software. Analysis of the secondary structure of the proteins were predicted by SOMPA online software. Using SWISS-MODEL online software constructed and analyzed the tertiary structure of the proteins. Using ABCpred, BepiPred, BCPred and SVMTrip online software analyzed linear B cell epitopes of proteins, The T cell dominant epitope of the protein was analyzed using SYFPEITHI, RANKPEP and IEDB online software. Omp2b was identified three linear B cell dominant epitopes, five CD8+ T cell dominant epitopes, and three CD4+ T cell dominant epitopes. P39 was identified three linear B cell dominant epitopes, two CD8+ T cell dominant epitopes, and two CD4+ T cell dominant epitopes. BLS was identified one linear B cell dominant epitope, one CD8+ T cell dominant epitope, and two CD4+ T cell dominant epitopes. The results indicated that epitope prediction of three Brucella vaccine candidate proteins can provide a theoretical basis for the construction of an ideal multivalent epitope vaccine against Brucella.

Functional Annotation and Epitope Prediction of Hypothetical Proteins of Mycobacterium tuberculosis H37Rv: An Immunoinformatics Approach

High-throughput genome sequencing technologies are revolutionizing bacterial genomics, resulting in the accumulation of 'unknown' or 'hypothetical' or ‘conserved hypothetical’ genes. However, approximately 40-50% of genes within a genome are often labeled as ‘hypothetical’ or ‘conserved hypothetical’ or 'unknown' whose function has not yet been established, inviting the functional annotation of these 'unknown genes'. Mycobacterium tuberculosis H37Rv has 3,924 protein coding genes, of which 606 proteins are classified as ‘unknown proteins’. We here predict reliable functional annotation by integrating several bioinformatics annotation tools, sequential BLAST homology searches, InterProScan searches, Gene Ontology (GO) mapping, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and established the putative function of 522 proteins with at least some functional annotations. The identified pathways from ‘unknown proteins’ are mapped to well-known pathways, and would provide many putative targets for the rational design of more effective anti-mycobacterial agents. In this work, we have computationally defined T cell epitopes of proteins of M. tuberculosis H37Rv to help in the design of a vaccine with haplotype specificity for a target population. The peptides of M. tuberculosis H37Rv which are predicted to bind different HLAs class-I (Human Leukocyte Antigens), do not show similarity with peptides of human proteome. Some of the nonameric peptides are promiscuous in their association with multiple alleles, and are considered for vaccine design because of their relevance in the wider coverage of human population. Altogether, functional annotations performed by integrative bioinformatics approaches should considerably enhance the interpretation of the unknown proteins of this medically important organism.

Paucity of functional CTL epitopes in the E7 oncoprotein of cervical cancer associated human papillomavirus type 16.

Many specific antiviral and antitumour immune responses have been attributed to the protective effects of antigen-specific CD8+ cytotoxic T lymphocytes (CTL). Recognition of virus infected or tumour cells by CTL requires presentation of at least one peptide epitope from a virus or tumour-specific antigen by the relevant MHC Class I molecule. Viral genes with mutations which remove CTL epitopes may thus be favoured for survival. Human cervical cancers are caused by papillomavirus infection, and these cancers consistently express the E7 protein of the oncogenic papillomavirus. We therefore investigated the MHC Class I restricted T cell epitopes of the human papillomavirus type 16 E7 oncoprotein using mice of five different genetic backgrounds, and an IFN-gamma ELISPOT assay, to determine the frequency with which MHC Class I epitopes might be expected in this small oncoprotein (98 amino acids). No MHC Class I restricted responses were detected in E7 immunized BALB/c (H-2d), CBA/CaH (H-2 k), FVB/N (H-2q) or A2KbH2b human HLA2.1 transgenic mice. In C57BL/6 J (H-2b) mice, a previously identified single antigenic epitope was detected. Therefore, we conclude that there is a paucity of MHC Class I restricted T cell epitopes in HPV16 E7 protein because of its small size. This might be advantageous to the virus. Furthermore here we present a quick and easy method to exhaustively determine CD8 T cell epitopes in proteins using a unique set of overlapping 8, 9 and 10 mer synthetic peptides.

A BASIC microcomputer program for prediction of B and T cell epitopes in proteins

A BASIC microcomputer program (EPIPLOT) has been developed for predicting B and T cell antigenic sites in proteins from their primary structures. The program calculates and plots flexibility, hydrophilicity and antigenicity profiles using 13 different scales, chosen as those yielding the best predictions on proteins whose antigenic structures are known. T cell epitope prediction is based on published algorithms focused on amphiphilic structures and characteristic sequence patterns. The advantages of joint predictions in locating T cell antigenic sites are also discussed.