B cell Epitopes
The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope[1]. Similar to T cell epitopes, B cell epitopes can be divided into two groups: conformational or linear[1]. B cell epitopes are mainly conformational[2][3]. There are additional epitope types when the quaternary structure is considered[3]. Epitopes that are masked when protein subunits aggregate are called cryptotopes[3]. Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits[3]. Neotopes are not recognized once the subunits dissociate[3].
Epitope Mapping
T-Cell Epitopes
There are two main methods of predicting peptide-MHC binding: data-driven and structure-based[1]. Structure based methods model the peptide-MHC structure and require great computational power[1]. Data-driven methods have higher predictive performance than structure-based methods[1]. Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules[1]. By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells[4].
B-Cell Epitopes
There are two main methods of epitope mapping: either structural or functional studies[5]. Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy[5]. X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes[5]. Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex[5]. This method does not require crystal formation but can only work on small peptides and proteins[5]. Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles[5].
Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding[5]. Competition methods look to determine if two monoclonal antibodies (mABs) can bind to an antigen at the same time or compete with each other to bind at the same site[5].
Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes[5]. If there’s a loss of antibody binding due to the substitution, the residue was likely a part of the epitope[5]. B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools[5].
Epitope-based vaccines
The first epitope-based vaccine was developed in 1985 by Jacob et al[6]. Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes[6]. These vaccines can use multiple epitopes to increase their efficacy[6]. Epitopes can have differential impacts on antibody production[7]. So, epitope choice can impact the efficacy of the vaccine[6]. To find epitopes to use for the vaccine, in silico mapping is often used[6]. Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency[6]. While epitope-based vaccines are generally safe, one possible side effect are cytokine storms[6].
- ^ a b c d e f Sanchez-Trincado, Jose L.; Gomez-Perosanz, Marta; Reche, Pedro A. (2017). "Fundamentals and Methods for T- and B-Cell Epitope Prediction". Journal of Immunology Research. 2017: 1–14. doi:10.1155/2017/2680160. ISSN 2314-8861. PMC 5763123. PMID 29445754.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ EL-Manzalawy, Yasser; Honavar, Vasant (2010). "Recent advances in B-cell epitope prediction methods". Immunome Research. 6 (Suppl 2): S2. doi:10.1186/1745-7580-6-S2-S2. ISSN 1745-7580. PMC 2981878. PMID 21067544.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b c d e Schutkowski, Mike; Reineke, Ulrich, eds. (2009). Epitope Mapping Protocols. Methods in Molecular Biology™. Vol. 524. Totowa, NJ: Humana Press. doi:10.1007/978-1-59745-450-6. ISBN 978-1-934115-17-6.
- ^ Peters, Bjoern; Nielsen, Morten; Sette, Alessandro (2020-04-26). "T Cell Epitope Predictions". Annual Review of Immunology. 38 (1): 123–145. doi:10.1146/annurev-immunol-082119-124838. ISSN 0732-0582.
- ^ a b c d e f g h i j k Potocnakova, Lenka; Bhide, Mangesh; Pulzova, Lucia Borszekova (2016-12-29). "An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction". Journal of Immunology Research. doi:10.1155/2016/6760830. PMC 5227168. PMID 28127568. Retrieved 2020-11-04.
{{cite web}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b c d e f g Parvizpour, Sepideh; Pourseif, Mohammad M.; Razmara, Jafar; Rafi, Mohammad A.; Omidi, Yadollah (2020-06-01). "Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches". Drug Discovery Today. 25 (6): 1034–1042. doi:10.1016/j.drudis.2020.03.006. ISSN 1359-6446.
- ^ "An overview of bioinformatics tools for epitope prediction: Implications on vaccine development". Journal of Biomedical Informatics. 53: 405–414. 2015-02-01. doi:10.1016/j.jbi.2014.11.003. ISSN 1532-0464.