with the
variable domains shown in blue, and the CDRs (which are part of the variable domains) in light blue. There are three CDRs (CDR1, CDR2 and CDR3), arranged non-consecutively, on the
amino acid sequence of a
variable domain of an antigen receptor. Three can be found on the Light-chain, named L1 through L3, and three on the Heavy-chain, named H1 through H3. Since the antigen receptors are typically composed of two variable domains (on two different polypeptide chains,
heavy and
light chain), there are six CDRs for each antigen receptor that can collectively come into contact with the antigen. A typical
monoclonal 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 molecule, which is composed of five antibodies and has increased avidity as a result of the collective affinity of all antigen-binding sites combined. Since most sequence variation associated with immunoglobulins and T cell receptors are found in the CDRs, these regions are sometimes referred to as
hypervariable regions. 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 V region sequence undergoes rearrangement during B-cell development, called
somatic recombination. This rearrangement of the V-region is where the CDR-L3 and CDR-H3 are encoded and diversified, whereas the other four CDRs are generated in the germ-line. The diversification of the CDR-H3 will ultimately give antibodies their specificity, and ability to recognize antigens. Other factors contribute to the antibody-antigen interaction, including amino acid residues. Residues located in particular positions of a CDR loop are used to classify canonical structures. and more recently by North et al.
Homology modeling 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 ==