Molecular localization of human IgG anti-F(ab')2 reactivity with variable- and constant-region lambda light-chain epitopes.
Human IgG antibodies reacting with antigenic determinants on F(ab')2 fragments represent generic antiidiotypic antibodies present in the serum of normal individuals. Additionally, the titers of these antibodies in the sera of patients with systemic lupus erythematosus (SLE) are inversely related to disease activity. Because these autoantibodies recognize predominantly light chain-related epitopes, especially lambda type, we synthesized constant (C)lambda- and variable (V)lambda-related overlapping 7-mer peptides on polypropylene pins to determine anti-F(ab')2-reactive epitopes on human lambda light chains. ELISA reactivity of affinity-purified anti-F(ab')2 antibodies obtained from normal individuals and from patients with SLE, as well as murine anti-human light-chain monoclonal antibodies specific for C lambda and V lambda subgroup-related determinants, was tested using the overlapping 7-mers of human lambda light-chain sequence. The patterns of reactivity against C lambda-related peptides were similar in both normal and SLE-derived anti-F(ab')2 antibodies. However, reactivity profiles against V lambda-related peptides were distinctively different between the normal and the SLE-associated anti-F(ab')2 autoantibodies. A decrease in reactivity among the SLE IgG anti-F(ab')2 antibodies was noted for particular amino acid V lambda complementarity-determining region (CDR) residues, including glycine at positions 27 and 54, alanine at 16 and 37, and tyrosine at 28 and 91. This different pattern of reactivity from normal may indicate that in SLE there is a failure of antiidiotypic control mechanisms, as reflected by a defect in production of antibody to immunodominant V lambda CDR residues.
Williams
R C
RC
Department of Medicine, University of Florida, Gainesville 32610, USA.
Malone
C C
CC
Silvestris
F
F
Solomon
A
A
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry*; D000915:Antibody Affinity; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology*; D005998:Glycine / Q000737:chemistry; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000737:chemistry*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry*; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D000409:Alanine; D005998:Glycine