title: Comparison of surface accessible residues in human and murine immunoglobulin Fv domains. Implication for humanization of murine antibodies.
abstract: Statistical analysis of a database of unique human and murine immunoglobulin heavy chain and light chain variable regions reveals that the precise patterns of exposed residues are different in human and murine antibodies, while most individual surface positions have strong preferences for a small number of residue types. Consideration of these surface patterns alone generates almost identical family groupings for light and heavy chain variable domain sequences to those produced by methods such as those of Kabat et al., where N-terminal framework sequences only are compared, or Tomlinson et al., in which entire variable region nucleotide sequences are used. This unexpected result suggests that the surfaces of V-regions are at least as well conserved as the core framework sequences. Furthermore, using these patterns of human and murine surface residues a novel method for the "humanization" of murine antibodies has been developed and tested.
authors.affiliation: Department of Biochemistry, University of Bath, Claverton Down, U.K.
authors.forename: J T
authors.initials: JT
authors.lastname: Pedersen
authors.forename: A H
authors.initials: AH
authors.lastname: Henry
authors.forename: S J
authors.initials: SJ
authors.lastname: Searle
authors.forename: B C
authors.initials: BC
authors.lastname: Guild
authors.forename: M
authors.initials: M
authors.lastname: Roguska
authors.forename: A R
authors.initials: AR
authors.lastname: Rees
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D051379:Mice; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013499:Surface Properties
chemical_list: D000939:Epitopes; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; C055966:immunoglobulin Fv; D009113:Muramidase