title: A molecular and structural analysis of the VH and VK regions of monoclonal antibodies bearing the A48 regulatory idiotype.
abstract: The results presented in this paper explore the molecular basis for expression of the A48 regulatory Id (RI). A48 RI+ mAb derived from idiotypically manipulated mice molecularly resembled the A48 and UPC 10 prototypes of this system by utilizing a VHX24-Vk10 combination. Id expression by these antibodies was not restricted by a particular D region sequence, JH, or JK segment, but quantitative differences in Id expression were associated with utilization of different members of the VK10 germ-line gene families. The VL sequences of these A48 RI+ mAb has identified amino acid residues lying in four different idiotope-determining regions which may contribute to the structural correlate of this Id. A comparative sequence analysis of the VH regions of these VHX24 utilizing A48 RI+ mAb with several A48 RI+ mAb utilizing VHJ558 or VH7183 VH genes as well as a hybrid transfectoma antibody derived from two A48 RI-, VHJ558 utilizing hybridomas, all suggested that four nonconsecutive positions which lie outside the idiotope-determining regions may contribute structural elements toward expression of this Id. The VH and VL regions of the A48RI+, VHX24-Vk 10+ mAb showed low to moderate levels of somatic mutation which showed different patterns of distribution between the complementary determining region (CDR) and framework regions in the H and L chains. Although the VK sequences contained 50% of the replacement mutations in the CDR, with a replacement/silent mutation ratio of 10, the CDR of the VH sequences contained only 31% of the replacement mutations with a replacement/silent mutation ratio of 0.69.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
authors.forename: C
authors.initials: C
authors.lastname: Victor-Kobrin
authors.forename: Z T
authors.initials: ZT
authors.lastname: Barak
authors.forename: F A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: B
authors.initials: B
authors.lastname: Kobrin
authors.forename: I
authors.initials: I
authors.lastname: Sanz
authors.forename: D
authors.initials: D
authors.lastname: French
authors.forename: J
authors.initials: J
authors.lastname: Rothe
authors.forename: C
authors.initials: C
authors.lastname: Bona
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics*; D001483:Base Sequence; D005630:Fructans / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D000911:Antibodies, Monoclonal; D005630:Fructans; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains