The effect of isotype and the J kappa region on antigen binding and idiotype expression by antibodies binding alpha (1----6) dextran.
Gene transfection and expression techniques have been used to produce three antibodies specific for alpha (1----6) linked dextran B512 with altered isotypes and J kappa regions. Expression of the L chain V region joined to J kappa 4 or J kappa 5 instead of to J kappa 2 reduced or abolished dextran binding. One antidextran with a reduced binding constant for dextran had the same combining site size as the parental mAb. Transfectoma Ig unreactive with dextran B512 did not bind to other class I or class II dextrans. Antibodies with J kappa 4-containing L chains expressed the 10.16.1 (anti-alpha(1----6) dextran) idiotype. In contrast variants expressing L chains with J kappa 5 lost idiotype expression, except when oligosaccharide is present on VH; all antibodies with J kappa 5 L chains continued to bind dextran but with reduced affinity. The presence of carbohydrate in VH may alter the conformation of both paratope and idiotope. Alteration of H chain isotype did not appear to significantly alter the ability of the antidextran to bind Ag; an exception may be that switching V regions to the IgM C region may decrease the apparent affinity for Ag.
Wallick
S C
SC
Department of Microbiology, Columbia University College of Physicians and Surgeons, NY 10032.
Kabat
E A
EA
Morrison
S L
SL
D000818:Animals; D000915:Antibody Affinity; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003911:Dextrans / Q000276:immunology / Q000378:metabolism*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000502:physiology*; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000502:physiology*; D007133:Immunoglobulin Joining Region / Q000235:genetics / Q000502:physiology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000032:analysis; D014162:Transfection
D003911:Dextrans; D007127:Immunoglobulin Constant Regions; D007130:Immunoglobulin Idiotypes; D007132:Immunoglobulin Isotypes; D007133:Immunoglobulin Joining Region; D007145:Immunoglobulin kappa-Chains; D011971:Receptors, Immunologic; C041999:alpha-1,6-dextran; C036109:dextran receptor