Epitope
Encyclopedia
An epitope, also known as antigenic determinant, is the part of an antigen
that is recognized by the immune system
, specifically by antibodies
, B cell
s, or T cell
s. The part of an antibody that recognizes the epitope is called a paratope
. Although epitopes are usually thought to be derived from non-self proteins, sequences derived from the host that can be recognized are also classified as epitopes.
The epitopes of protein
antigens are divided into two categories, conformational epitope
s and linear epitope
s, based on their structure and interaction with the paratope. A conformational epitope is composed of discontinuous sections of the antigen's amino acid
sequence. These epitopes interact with the paratope based on the 3-D surface features and shape or tertiary structure
of the antigen. Most epitopes are conformational.
By contrast, linear epitopes interact with the paratope based on their primary structure
. A linear epitope is formed by a continuous sequence of amino acids from the antigen.
epitopes are presented on the surface of an antigen-presenting cell
, where they are bound to MHC
molecules. 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, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
). 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.
using protein microarray
s, and with the ELISPOT
or ELISA
techniques.
Intensive research is currently taking place to design reliable tools that will predict epitopes on proteins.
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 localization, purification, and further molecular characterization. Common epitopes used for this purpose are Myc-tag
, HA-tag, FLAG-tag
, GST-tag, 6xHis
and OLLAS .
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
that is recognized by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, specifically by antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s, or T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s. The part of an antibody that recognizes the epitope is called a paratope
Paratope
The paratope is the part of an antibody which recognises an antigen, the antigen-binding site of an antibody. It is a small region of the antibody's Fv region and contains parts of the antibody's heavy and light chains....
. Although epitopes are usually thought to be derived from non-self proteins, sequences derived from the host that can be recognized are also classified as epitopes.
The epitopes of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
antigens are divided into two categories, conformational epitope
Conformational epitope
A conformational epitope is a sequence of subunits composing an antigen that come in direct contact with a receptor of the immune system.An antigen is any substance that the immune system can recognize as foreign...
s and linear epitope
Linear epitope
A linear or a sequential epitope is an epitope that is recognized by antibodies by its linear sequence of amino acids, or primary structure. In contrast, most antibodies recognize a conformational epitope that has a specific three-dimensional shape and its protein structure.An antigen is any...
s, based on their structure and interaction with the paratope. A conformational epitope is composed of discontinuous sections of the antigen's amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence. These epitopes interact with the paratope based on the 3-D surface features and shape or tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
of the antigen. Most epitopes are conformational.
By contrast, linear epitopes interact with the paratope based on their primary structure
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
. A linear epitope is formed by a continuous sequence of amino acids from the antigen.
T cell epitopes
T cellT cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
epitopes are presented on the surface of an antigen-presenting cell
Antigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
, where they are bound to MHC
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
molecules. 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, and non-classical MHC molecules also present non-peptidic epitopes such as glycolipids.
Cross-reactivity
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 JerneNiels Kaj Jerne
Niels Kaj Jerne, FRS was a Danish immunologist. He was awarded the Nobel Prize in Physiology or Medicine in 1984. The citation read "For theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies"....
). 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 mappedEpitope mapping
Epitope mapping is the process of identifying the binding sites, or ‘epitopes’, of antibodies on their target antigens .Identification and characterization of the binding sites of antibodies can aid in the discovery and development of new therapeutics, vaccines, and diagnostics.Epitopes can be...
using protein microarray
Protein microarray
A protein microarray, sometimes referred to as a protein binding microarray,provides a multiplex approach to identify protein–protein interactions, to identify the substrates of protein kinases, to identify transcription factor protein-activation, or to identify the targets of biologically active...
s, and with the ELISPOT
ELISPOT
The Enzyme-linked immunosorbent spot assay is a common method for monitoring immune responses in humans and animals. It was developed by Cecil Czerkinsky in 1983....
or ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
techniques.
Intensive research is currently taking place to design reliable tools that will predict epitopes on proteins.
Epitope tags
Epitopes are often used in proteomicsProteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
and the study of other gene products. Using recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
techniques genetic sequences coding for epitopes that are recognized by common antibodies can be fused to the gene. Following synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
, the resulting epitope tag allows the antibody to find the protein or other gene product enabling lab techniques for localization, purification, and further molecular characterization. Common epitopes used for this purpose are Myc-tag
Myc-tag
A myc tag is a polypeptide protein tag derived from the c-myc gene product that can be added to a protein using recombinant DNA technology. It can be used for affinity chromatography, then used to separate recombinant, overexpressed protein from wild type protein expressed by the host organism...
, HA-tag, FLAG-tag
FLAG-tag
FLAG-tag, or FLAG octapeptide, is a polypeptide protein tag that can be added to a protein using recombinant DNA technology. It can be used for affinity chromatography, then used to separate recombinant, overexpressed protein from wild-type protein expressed by the host organism...
, GST-tag, 6xHis
Polyhistidine-tag
A polyhistidine-tag is an amino acid motif in proteins that consists of at least five histidine residues, often at the N- or C-terminus of the protein. It is also known as hexa histidine-tag, 6xHis-tag, and by the trademarked name His-tag...
and OLLAS .
See also
- ParatopeParatopeThe paratope is the part of an antibody which recognises an antigen, the antigen-binding site of an antibody. It is a small region of the antibody's Fv region and contains parts of the antibody's heavy and light chains....
- MimotopeMimotopeA mimotope is a macromolecule, often a peptide, which mimics the structure of an epitope. Because of this property it causes an antibody response similar to the one elicited by the epitope. An antibody for a given epitope antigen will recognize a mimotope which mimics that epitope. Mimotopes are...
- Epitope mappingEpitope mappingEpitope mapping is the process of identifying the binding sites, or ‘epitopes’, of antibodies on their target antigens .Identification and characterization of the binding sites of antibodies can aid in the discovery and development of new therapeutics, vaccines, and diagnostics.Epitopes can be...
- Conformational epitopeConformational epitopeA conformational epitope is a sequence of subunits composing an antigen that come in direct contact with a receptor of the immune system.An antigen is any substance that the immune system can recognize as foreign...
- Polyclonal B cell responsePolyclonal B cell responsePolyclonal B cell response is a natural mode of immune response exhibited by the adaptive immune system of mammals. It ensures that a single antigen is recognized and attacked through its overlapping parts, called epitopes, by multiple clones of B cell....
- Odotope
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 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