User:MicrobiologyKat2020/Epitope

B cell Epitopes

The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope. Similar to T cell epitopes, B cell epitopes can be divided into two groups: conformational or linear. B cell epitopes are mainly conformational. There are additional epitope types when the quaternary structure is considered. Epitopes that are masked when protein subunits aggregate are called cryptotopes. Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits. Neotopes are not recognized once the subunits dissociate.

Epitope Mapping

T-Cell Epitopes

There are two main methods of predicting peptide-MHC binding: data-driven and structure-based. Structure based methods model the peptide-MHC structure and require great computational power. Data-driven methods have higher predictive performance than structure-based methods. Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules. By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.

B-Cell Epitopes

There are two main methods of epitope mapping: either structural or functional studies. Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy. X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes. Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex. This method does not require crystal formation but can only work on small peptides and proteins. Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.

Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding. 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.

Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes. If there’s a loss of antibody binding due to the substitution, the residue was likely a part of the epitope. B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.

Epitope-based vaccines

The first epitope-based vaccine was developed in 1985 by Jacob et al. Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes. These vaccines can use multiple epitopes to increase their efficacy. Epitopes can have differential impacts on antibody production. So, epitope choice can impact the efficacy of the vaccine. To find epitopes to use for the vaccine, in silico mapping is often used. Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency. While epitope-based vaccines are generally safe, one possible side effect are cytokine storms.