title: Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex.
abstract: Although antibodies are highly specific, cross-reactions are frequently observed. To understand the molecular basis of this phenomenon, we studied the anti-hen egg lysozyme (HEL) monoclonal antibody (mAb) D11.15, which cross-reacts with several avian lysozymes, in some cases with a higher affinity (heteroclitic binding) than for HEL. We have determined the crystal structure of the Fv fragment of D11.15 complexed with pheasant egg lysozyme (PHL). In addition, we have determined the structure of PHL, Guinea fowl egg lysozyme, and Japanese quail egg lysozyme. Differences in the affinity of D11.15 for the lysozymes appear to result from sequence substitutions in these antigens at the interface with the antibody. More generally, cross-reactivity is seen to require a stereochemically permissive environment for the variant antigen residues at the antibody-antigen interface.
authors.affiliation: Unité d'Immunologie Structurale (Centre National de la Recherche Scientifique, Unité de Recherches Associée URA 359), Institut Pasteur, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Chitarra
authors.forename: P M
authors.initials: PM
authors.lastname: Alzari
authors.forename: G A
authors.initials: GA
authors.lastname: Bentley
authors.forename: T N
authors.initials: TN
authors.lastname: Bhat
authors.forename: J L
authors.initials: JL
authors.lastname: Eiselé
authors.forename: A
authors.initials: A
authors.lastname: Houdusse
authors.forename: J
authors.initials: J
authors.lastname: Lescar
authors.forename: H
authors.initials: H
authors.lastname: Souchon
authors.forename: R J
authors.initials: RJ
authors.lastname: Poljak
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D002645:Chickens; D003370:Coturnix; D003429:Cross Reactions; D003460:Crystallization; D005260:Female; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D009113:Muramidase