Antibody molecules are highly antigen-specific receptors of the immune system. Antigen-antibody interaction involves the antibody VL and VH domains, each composed of a framework whose structure is well conserved . The antigen-binding site is composed of six hypervariable loops, three from the VL domain and three from the VH domain: L1, L2, L3, and HI, H2, H3, respectively . Genetically, L1 and L2 are encoded by the VL gene, while L3 is produced by the recombination of an additional gene segment, JL. In a similar way, H1 and H2 are encoded by the VH gene, and H3 is a result of the recombination of two additional gene segments, D and JH .
Analysis of antibodies of known atomic structure has revealed a small number of main-chain conformations or canonical structures for L1, L2, and L3, as well as for H1 and H2 . Canonical structures in five of six hypervariable loops imply that only a few main-chain conformations are present in a large set of antibody molecules with different loop sequences. Examination of the known human IGHV, IGKV, and IGLV functional germline genes indicates that most of these sequences have canonical structures . This finding provides evidence concerning structural restrictions at work in the process of antigen recognition .
In addition to the human V functional germline genes, V pseudogenes amount to roughly 40% of the total number of human V genes