![Complementarity determining regions](https://upload.wikimedia.org/wikipedia/commons/3/3c/Complementarity_determining_regions.PNG)
Complementarity-determining regions (CDRs) are part of the variable chains in
immunoglobulins
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
(antibodies) and
T cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...
s, generated by
B-cells
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...
and
T-cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
respectively, where these molecules bind to their specific antigen. A set of CDRs constitutes a
paratope
In immunology, a paratope, also known as an antigen-binding site, is the part of an antibody which recognizes and binds to an antigen. It is a small region at the tip of the antibody's antigen-binding fragment and contains parts of the antibody' ...
. As the most variable parts of the molecules, CDRs are crucial to the diversity of antigen specificities generated by
lymphocytes
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
.
Location and structure
![Antibody with CDRs](https://upload.wikimedia.org/wikipedia/commons/7/79/Antibody_with_CDRs.svg)
There are three CDRs (CDR1, CDR2 and CDR3), arranged non-consecutively, on the
amino acid sequence
Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...
of a
variable domain
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
of an antigen receptor. Since the antigen receptors are typically composed of two variable domains (on two different polypeptide chains,
heavy
Heavy may refer to:
Measures
* Heavy (aeronautics), a term used by pilots and air traffic controllers to refer to aircraft capable of 300,000 lbs or more takeoff weight
* Heavy, a characterization of objects with substantial weight
* Heavy, ...
and
light chain), there are six CDRs for each antigen receptor that can collectively come into contact with the antigen. A single antibody molecule has two antigen receptors and therefore contains twelve CDRs total. There are three CDR loops per variable domain in antibodies. Sixty CDRs can be found on a pentameric
IgM
Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...
molecule.
Since most sequence variation associated with immunoglobulins and T cell receptors are found in the CDRs, these regions are sometimes referred to as ''
hypervariable region
A hypervariable region (HVR) is a location within nuclear DNA or the D-loop of mitochondrial DNA in which base pairs of nucleotides repeat (in the case of nuclear DNA) or have substitutions (in the case of mitochondrial DNA). Changes or repeats in ...
s''. Within the variable ''domain'', CDR1 and CDR2 are found in the variable (V) ''region'' of a polypeptide chain, and CDR3 includes some of V, all of diversity (D, heavy chains only) and joining (J) regions. CDR3 is the most variable.
The
tertiary structure
Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...
of an antibody is important to analyze and design new antibodies. The three-dimensional structures of the non-H3 CDRs of antibodies have been clustered and classified by Chothia et al. and more recently by North et al.
Homology modeling
Homology modeling, also known as comparative modeling of protein, refers to constructing an atomic-resolution model of the "''target''" protein from its amino acid sequence and an experimental three-dimensional structure of a related homologous pr ...
is a computational method to build tertiary structures from amino-acid sequences. The so-called H3-rules are empirical rules to build models of CDR3.
See also
*
Framework region
In molecular biology, a framework region is a subdivision of the variable region (Fab) of the antibody. The variable region is composed of seven amino acid regions, four of which are framework regions and three of which are hypervariable regions. ...
*
Hypervariable region
A hypervariable region (HVR) is a location within nuclear DNA or the D-loop of mitochondrial DNA in which base pairs of nucleotides repeat (in the case of nuclear DNA) or have substitutions (in the case of mitochondrial DNA). Changes or repeats in ...
References
External links
* {{MeshName, Complementarity+determining+regions
PyIgClassify -- server for classification of CDR conformations
Amino acids
Antibodies
Immunology