paratopes

Paratopes are the antigen-binding sites of antibodies and T cell receptors. They are the parts of the receptor that contact epitopes, the specific regions on antigens recognized by the immune receptor. In antibodies, each molecule has two identical paratopes, located at the ends of the Fab arms; in T cell receptors, paratopes arise from the variable regions of the alpha and beta chains. The paratope is formed primarily by the hypervariable loops, the complementarity-determining regions (CDRs), within the variable domains (VH and VL for antibodies). The residues in the CDRs contribute most of the contact with the antigen, while framework residues provide structural support.

Paratopes recognize epitopes through a combination of shape complementarity and chemical interactions, including hydrogen bonds, ionic interactions, van der Waals forces, and hydrophobic contacts. Binding is noncovalent and reversible. The specificity and affinity of a paratope are shaped during B cell development and immune responses by V(D)J recombination, junctional diversity, and somatic hypermutation, a process known as affinity maturation.

Paratopes and their corresponding epitopes are complementary; an epitope is the antigenic determinant on the antigen, whereas the paratope is the corresponding binding site on the receptor. Paratopes can recognize both linear and conformational epitopes, with conformational epitopes requiring proper three-dimensional folding of the antigen. In research and medicine, paratope mapping and understanding paratope-epitope interactions inform antibody engineering, vaccine design, and therapeutic development.