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. 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. 90% of epitopes are conformational.

Function

T cell epitopes

T cell epitopes 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, 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. B cell epitopes can be divided into two groups: conformational or linear. There are additional epitope types when the quaternary structure is considered. although not all in-silico T cell epitope prediction algorithms are equivalent in their accuracy. There are two main methods of predicting peptide-MHC binding: data-driven and structure-based.

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. Mutagenesis uses randomly/site-directed mutations at individual residues to map epitopes.

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 including identifying the protein's binding partners.

Common epitopes used for this purpose are Myc-tag, HA-tag, FLAG-tag, GST-tag, 6xHis, V5-tag and OLLAS. An epitope tag was first described by Munro and Pelham to detect and track proteins in 1984 . Tags were quickly adapted for purifying proteins and to detect, pull down, and clone interaction partners of proteins . These tags were originally referred to as "peptide tag", "epitope insertion", "marker sequence", and "epitope addition" , until "epitope tag" was coined and popularized.

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 development of "epitope-focused" vaccine design.

Epitope-based vaccines

The first epitope-based vaccine was developed in 1985 by Chaim Jacob and colleagues from The Weizmann Institute of Science. Epitope-based vaccines stimulate humoral and cellular immune responses using isolated B-cell or T-cell epitopes. 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.

See also

  • Cryptotope
  • Epitope binning
  • Mimotope
  • Odotope
  • Polyclonal B cell response
  • Protein tag
  • TimeSTAMP protein labelling

References

  • 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

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

it:Antigene#Epitopo