Polymorphism in V kappa 10 genes encoding L chains of antibodies bearing the Ars-A and A48 cross-reactive idiotypes.
p-azophenylarsonate-specific antibodies of A/J mice which bear the Ars-A crossreactive idiotype utilize the V kappa-Ars-A gene segment, a member of the V kappa 10 family. Southern hybridization of genomic DNA from several inbred strains using a probe from the 5' flanking region of the V kappa-Ars-A gene demonstrated three patterns of restriction fragment length polymorphisms (RFLP). Six genes corresponding to hybridizing bands were obtained from DNA libraries of C.AKR, PERU and A/J mice, and nucleotide sequence comparisons revealed two allelic groups: AKR1 (Igk-V10.1a), AJ1 (Igk-V10.1b) and PERU1 (Igk-V10.1c); AKR2 (Igk-V10.2a), AJ2 (Igk-V10.2b), and PERU2 (Igk-V10.2c). The Igk-V10.1b gene of the A/J strain is the V kappa-Ars-A gene used in Ars-A idiotype-positive antibodies. The product of the C.AKR allele (Igk-V10.1a) contained four amino acid substitutions in CDR3 as compared with Igk-V10.1b. These substitutions probably explain the failure of AKR mice and other strains with the same V kappa 10 RFLP pattern to provide in genetic crosses a L chain which, together with the A/J VH-ArsA gene product, form Ars-A idiotype-positive antibodies. Also, the nucleotide sequence identity between the Igk-V10.1c and Igk-V10.1b alleles and the Igk-V10.2c and Igk-V10.2b alleles is significantly greater than that seen in comparisons with the Igk-V10.1a and Igk-V10.2a alleles, respectively, suggesting an evolutionary pathway similar to that of the linked Igk-J locus. BALB/c antibodies bearing the A48 regulatory idiotype contain L chains encoded by the BALB/c Igk-V10.1b and Igk-V10.2b alleles. Strongly A48 idiotype-positive antibodies utilize the Igk-V10.1b chain, and weakly A48-positive antibodies use the Igk-V10.2b L chain. The possible effects of amino acid substitutions specified by the Igk-V10.1a, Igk-V10.1c, Igk-V10.2a, and Igk-V10.2c alleles on their ability to provide L chains used in A48 idiotype-positive antibodies are discussed.
Kim
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Department of Microbiology, University of Texas, Austin 78712.
Sanz
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Williams
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Capra
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Gottlieb
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D003429:Cross Reactions; D005803:Genes, Immunoglobulin; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A / Q000235:genetics; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D010132:p-Azobenzenearsonate / Q000276:immunology
D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010132:p-Azobenzenearsonate