Epitope
An epitope, also known as antigenic determinant, is the part of an
The epitopes of
Function
T cell epitopes
T cell epitopes[9] are presented on the surface of an antigen-presenting cell, where they are bound to major histocompatibility complex (MHC) molecules. In humans, professional antigen-presenting cells are specialized to present MHC class II peptides, whereas most nucleated somatic cells present MHC class I peptides. T cell epitopes presented by MHC class I molecules are typically peptides between 8 and 11 amino acids in length, whereas MHC class II molecules present longer peptides, 13–17 amino acids in length,[10] and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
B cell epitopes
The part of the antigen that immunoglobulin or antibodies bind to is called a B-cell epitope.[11] B cell epitopes can be divided into two groups: conformational or linear.[11] B cell epitopes are mainly conformational.[12][13] There are additional epitope types when the quaternary structure is considered.[13] Epitopes that are masked when protein subunits aggregate are called cryptotopes.[13] Neotopes are epitopes that are only recognized while in a specific quaternary structure and the residues of the epitope can span multiple protein subunits.[13] Neotopes are not recognized once the subunits dissociate.[13]
Cross-activity
Epitopes are sometimes cross-reactive. This property is exploited by the immune system in regulation by anti-idiotypic antibodies (originally proposed by Nobel laureate Niels Kaj Jerne). If an antibody binds to an antigen's epitope, the paratope could become the epitope for another antibody that will then bind to it. If this second antibody is of IgM class, its binding can upregulate the immune response; if the second antibody is of IgG class, its binding can downregulate the immune response.[citation needed]
Epitope mapping
T cell epitopes
MHC class I and II epitopes can be reliably predicted by computational means alone,[14] although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.[15] There are two main methods of predicting peptide-MHC binding: data-driven and structure-based.[11] Structure based methods model the peptide-MHC structure and require great computational power.[11] Data-driven methods have higher predictive performance than structure-based methods.[11] Data-driven methods predict peptide-MHC binding based on peptide sequences that bind MHC molecules.[11] By identifying T-cell epitopes, scientists can track, phenotype, and stimulate T-cells.[16][17]
B cell epitopes
There are two main methods of epitope mapping: either structural or functional studies.[18] Methods for structurally mapping epitopes include X-ray crystallography, nuclear magnetic resonance, and electron microscopy.[18] X-ray crystallography of Ag-Ab complexes is considered an accurate way to structurally map epitopes.[18] Nuclear magnetic resonance can be used to map epitopes by using data about the Ag-Ab complex.[18] This method does not require crystal formation but can only work on small peptides and proteins.[18] Electron microscopy is a low-resolution method that can localize epitopes on larger antigens like virus particles.[18]
Methods for functionally mapping epitopes often use binding assays such as western blot, dot blot, and/or ELISA to determine antibody binding.[18] 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.[18] Another technique involves high-throughput mutagenesis, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.[19] Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes.[18] B-cell epitope mapping can be used for the development of antibody therapeutics, peptide-based vaccines, and immunodiagnostic tools.[18][20]
Epitope tags
Epitopes are often used in
Epitope-based vaccines
The first epitope-based vaccine was developed in 1985 by Jacob et al.[26] Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes.[26][20][17] These vaccines can use multiple epitopes to increase their efficacy.[26] To find epitopes to use for the vaccine, in silico mapping is often used.[26] Once candidate epitopes are found, the constructs are engineered and tested for vaccine efficiency.[26] While epitope-based vaccines are generally safe, one possible side effect is cytokine storms.[26]
Neoantigenic determinant
A neoantigenic determinant is an epitope on a
See also
- Cryptotope
- Epitope binning
- Mimotope
- Odotope
- Polyclonal B cell response
- Protein tag
- TimeSTAMP protein labelling
References
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- ^ PMID 28127568.
- PMID 24854488.
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- ISBN 978-1603273749.
- ^ Novus, Biologicals. "OLLAS Epitope Tag". Novus Biologicals. Retrieved 23 November 2011.
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- PMID 24499818.
- PMID 27085173.
- ^ S2CID 214629963.
- ISBN 978-3540441724.
- ^ Neoantigen. (n.d.) Mosby's Medical Dictionary, 8th edition. (2009). Retrieved February 9, 2015 from Medical Dictionary Online
External links
- Antibodies bind to conformational shapes on the surfaces of antigens (Janeway Immunobiology Section 3.8)
- Antigens can bind in pockets or grooves, or on extended surfaces in the binding sites of antibodies (Janeway Immunobiology Figure 3.8)
Epitope prediction methods
- Rubinstein ND, Mayrose I, Martz E, Pupko T (September 2009). "Epitopia: a web-server for predicting B-cell epitopes". BMC Bioinformatics. 10: 287. PMID 19751513.
- Rubinstein ND, Mayrose I, Pupko T (February 2009). "A machine-learning approach for predicting B-cell epitopes". Molecular Immunology. 46 (5): 840–847. PMID 18947876.
- Saravanan V, Gautham N (October 2015). "Harnessing Computational Biology for Exact Linear B-Cell Epitope Prediction: A Novel Amino Acid Composition-Based Feature Descriptor". Omics. 19 (10): 648–658. PMID 26406767.
- Singh H, Ansari HR, Raghava GP (2013). "Improved method for linear B-cell epitope prediction using antigen's primary sequence". PLOS ONE. 8 (5): e62216. PMID 23667458.
Epitope databases
- MHCBN: A database of MHC/TAP binder and T-cell epitopes
- Bcipep: A database of B-cell epitopes
- SYFPEITHI – First online database of T cell epitopes
- IEDB – Database of T and B cell epitopes with annotation of recognition context – NIH funded
- ANTIJEN – T and B cell epitope database at the Jenner institute, UK
- IMGT/3Dstructure-DB – Three-dimensional structures of B and T cell epitopes with annotation of IG and TR – IMGT, Montpellier, France
- SEDB: A Structural Epitope Database – Pondicheery University, DIT funded
- Epitopes at the U.S. National Library of Medicine Medical Subject Headings (MeSH)