An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.
For example, the epitope is the specific piece of the antigen to which
an antibody binds. The part of an antibody that binds to the epitope is
called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.
The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation. The proportion of epitopes that are conformational is unknown.
The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation. The proportion of epitopes that are conformational is unknown.
Function
T cell epitopes
T cell epitopes are presented on the surface of an antigen-presenting cell, where they are bound to 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, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
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.
Epitope mapping
Epitopes can be mapped using protein microarrays, and with the ELISpot or ELISA techniques. Another technique involves high-throughput mutagenesis, an epitope mapping strategy developed to improve rapid mapping of conformational epitopes on structurally complex proteins.
MHC class I and II epitopes can be reliably predicted by computational means alone, although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy.
Epitope tags
Epitopes are often used in proteomics and the study of other gene products. Using recombinant DNA techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following synthesis,
the resulting epitope tag allows the antibody to find the protein or
other gene product enabling lab techniques for localisation,
purification, and further molecular characterization. Common epitopes
used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis, V5-tag and OLLAS. Peptides can also be bound by proteins that form covalent bonds to the peptide, allowing irreversible immobilisation These strategies have also been successfully applied to the develohttps://en.wikipedia.org/wiki/Epitopepment of "epitope-focused" vaccine design.
Neoantigenic determinant
A neoantigenic determinant is an epitope on a neoantigen, which is a newly formed antigen that has not been previously recognized by the immune system. Neoantigens are often associated with tumor antigens and are found in oncogenic cells.
Neoantigens and, by extension, neoantigenic determinants can be formed
when a protein undergoes further modification within a biochemical
pathway such as glycosylation, phosphorylation or proteolysis.
This, by altering the structure of the protein, can produce new
epitopes that are called neoantigenic determinants as they give rise to
new antigenic determinants. Recognition requires separate, specific antibodies.
