title: Insertions and deletions in hypervariable loops of antibody heavy chains contribute to molecular diversity.
abstract: Antibody diversity, a molecular feature which allows these proteins to specifically interact with a diverse set of targets, is created at the genetic level by a variety of means. These include germline gene segment recombination, junctional diversity and single basepair (bp) substitution. We here demonstrate that a human high affinity antibody specific for an exogenous protein antigen carry three amino acid residues immediately adjacent to the first hypervariable loop of the heavy chain. These additional residues are shown not to be encoded by the germline repertoire. We also describe the characteristics of insertions and deletions, not found in any known germline sequence, within the first and second hypervariable loops of other previously described antibody-encoding genes. These findings demonstrate that insertions or deletions of entire codons provide yet another approach by which the human antibody repertoire is diversified in vivo. Since these major genetic modifications occur within or immediately adjacent to loops contributing to the antigen-binding site, they are likely to affect the binding properties of the mutated antibodies.
authors.affiliation: Department of Immunotechnology, Lund University, Sweden. mats.ohlin@immun.lth.se
authors.forename: M
authors.initials: M
authors.lastname: Ohlin
authors.forename: C A
authors.initials: CA
authors.lastname: Borrebaeck
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000235:genetics; D000916:Antibody Diversity / Q000235:genetics*; D001483:Base Sequence; D004251:DNA Transposable Elements / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
chemical_list: D004251:DNA Transposable Elements; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region