The amino acid residues at the VH-D-JH junctions affect the affinity of anti-p-azophenylarsonate antibodies.
Murine A/J anti-p-azophenylarsonate (Ars) antibodies sharing a predominant idiotype are encoded by a single combination of germ-line V region gene segments. The dominance of this idiotype among secondary immune response anti-Ars antibodies has been explained by the Ag-driven selection of favorable somatic mutants of this gene segment combination, associated with an intrinsic Ars-affinity of the germ-line V region higher than that of other possible combinations. To determine the effect of junctional diversity upon affinity for Ag, independently of somatic mutation, we determined the V region sequences and affinity for Ars of five primary response antibodies. These antibodies share identical unmutated V regions but differ only at the D gene junctions. Among the five antibodies, Ars-affinity differed up to 10-fold depending upon the identity of the amino acid residues at the VH-D and the D-JH junctions. The combination of junctional residues observed in two primary response antibodies with relatively low Ars-affinity has not been observed among secondary response antibodies. Thus the identity of junctional residues resulting from gene rearrangement prior to antigen stimulation must be taken into account in hypotheses which account for idiotype dominance by selection on the basis of affinity.
Parhami-Seren
B
B
Department of Surgery, Massachusetts General Hospital, Boston.
Wysocki
L
L
Margolies
M N
MN
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000235:genetics; D000916:Antibody Diversity / Q000235:genetics; D001391:Azo Compounds / Q000276:immunology*; D001483:Base Sequence; D001667:Binding, Competitive; D007074:Immunoglobulin G / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007133:Immunoglobulin Joining Region / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D010132:p-Azobenzenearsonate / Q000276:immunology*
D001391:Azo Compounds; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D010132:p-Azobenzenearsonate