Structural and idiotypic characterization of the L chains of human IgM autoantibodies with different specificities.
We have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1. JK and CK genes did not show the same pattern of restriction. There is a good correlation between the amino acid sequence and the presence of the kIIIb marker. The idiotypic marker PSL2 was present in 34 out of 35 kIIIb L chains analyzed (97%) and the PSL3 in 27 (80%). Moreover, the hydrophilicity and antigenic profiles of these L chains corroborate the presence of the epitopes detected by the anti-CRI. These results demonstrate a restricted selection of the Vk genes used by a family of self reacting proteins, and an unusual evolutionary conservation of the idiotypic structure that may be involved in the network regulation.
Goñi
F R
FR
Department of Pathology, New York University Medical Center 10016.
Chen
P P
PP
McGinnis
D
D
Arjonilla
M L
ML
Fernandez
J
J
Carson
D
D
Solomon
A
A
Mendez
E
E
Frangione
B
B
D000373:Agglutinins; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000302:isolation & purification*; D003429:Cross Reactions; D003450:Cryoglobulins; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics / Q000302:isolation & purification*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000302:isolation & purification*; D007382:Intermediate Filaments / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D008969:Molecular Sequence Data; D012217:Rheumatoid Factor
D000373:Agglutinins; D001323:Autoantibodies; D003450:Cryoglobulins; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D008077:Lipoproteins, LDL; C029443:cold agglutinins; D012217:Rheumatoid Factor