CDR3

CDR3 stands for Complementarity-Determining Region 3, the most variable part of the variable domain in antigen receptors. It is generated during V(D)J recombination, when variable (V), diversity (D), and joining (J) gene segments are rearranged to form the final variable region. The CDR3 loop spans the junctions between these segments and, in antibody heavy chains and T-cell receptor beta chains, is created by V-D-J joining; in light chains and T-cell receptor alpha chains, it arises from V-J joining. Junctional diversity is further increased by exonuclease trimming and the addition of non-templated nucleotides by terminal deoxynucleotidyl transferase, producing a unique sequence for each lymphocyte.

Function and significance: The CDR3 loop contributes a major portion of the antigen-contact surface and largely determines specificity. In antibodies, CDR3 of the heavy chain (CDR3H) and, to a lesser extent, the light chain CDR3 influence epitope recognition. In T-cell receptors, CDR3 regions are critical for recognizing peptide antigens presented by MHC molecules, with their variability shaping specificity and cross-reactivity.

Applications: In immunology, CDR3 sequences are central to repertoire sequencing and clonotype analysis, used to monitor immune responses over time, assess diversity, and track clonal expansions in infections, vaccination, cancer immunotherapy, and transplantation.

Notes: While CDR3 is remarkably variable and informative, the other CDRs (CDR1 and CDR2) and the framework regions also contribute to binding. Different receptor types and species show characteristic differences in CDR3 length distributions.