Molecular characterization and structural modeling of immunoglobulin variable regions from murine monoclonal antibodies specific for hepatitis B virus surface antigen.
We have characterized structurally the V regions of a set of murine monoclonal antibodies designated A1.2, A3.1, and A2.1, which recognize a group-specific epitope associated with hepatitis B virus surface antigen (HBsAg). The selection of these antibodies for this characterization was based on data which indicated that A1.2 and A3.1 recognize an overlapping epitope, while A2.1 recognizes a different group-specific epitope, on the HBsAg molecule. In addition, a conformation-dependent cross reactive Id is expressed on both A1.2 and A3.1, but not on A2.1. We have determined the primary sequence structures of these three monoclonal antibodies to HBsAg (anti-HBs), and have aligned them to evaluate V region sequence homology and identify potential regions of structural homology which provide a basis for the HBsAg epitope recognition and the cross reactive Id. Both A1.2 and A3.1 express VH regions which are highly homologous to the VH NP gene family (V186-2), both use members of the DSP2 D region gene family and utilize the JH 2 and JH 1 J gene segments, respectively. Alternatively, A2.1 is related to the VH J558 gene family and expresses a fusion of the DFL16.1 and DQ52 D gene regions in conjunction with the MH 1 gene segment. Each of these three monoclonal anti-HBs utilize light chains from the V kappa 21 and the J kappa 4 gene families. Primary amino acid sequence data were employed to construct computer generated models of the A1.2, A3.1, and A2.1 V regions to determine potential antigen combining site structures and the basis for the expression of the cross reactive Id. These results are discussed in terms of potential interaction sites with HBsAg and V region sites involved in Id expression.
Lohman
K L
KL
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228-0147.
Kieber-Emmons
T
T
Kennedy
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D000918:Antibody Specificity; D001483:Base Sequence; D003198:Computer Simulation; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005803:Genes, Immunoglobulin; D006510:Hepatitis B Antibodies / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016018:Least-Squares Analysis; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains