Molecular localization of human IgG anti-F(ab′)2 reactivity with variable- and constant-region λ light-chain epitopes

Ralph C. Williams, Christine C. Malone, Franco Silvestris, Alan Solomon

Research output: Contribution to journalArticle

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Abstract

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 λ type, we synthesized constant (C)λ- and variable (V)λ-related overlapping 7-mer peptides on polypropylene pins to determine anti-F(ab′)2-reactive epitopes on human λ 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 Cλ and Vλ subgroup-related determinants, was tested using the overlapping 7-mers of human λ light-chain sequence. The patterns of reactivity against Cλ-related peptides were similar in both normal and SLE-derived anti-F(ab′)2 antibodies. However, reactivity profiles against Vλ-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 Vλ 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 Vλ CDR residues.

Original languageEnglish (US)
Pages (from-to)349-362
Number of pages14
JournalJournal of Clinical Immunology
Volume15
Issue number6
DOIs
StatePublished - Nov 1 1995

Fingerprint

Systemic Lupus Erythematosus
Epitopes
Light
Antibodies
Complementarity Determining Regions
Autoantibodies
Peptides
Polypropylenes
Serum
Alanine
Glycine
Antibody Formation
Tyrosine
anti-IgG
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies
Amino Acids

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Molecular localization of human IgG anti-F(ab′)2 reactivity with variable- and constant-region λ light-chain epitopes. / Williams, Ralph C.; Malone, Christine C.; Silvestris, Franco; Solomon, Alan.

In: Journal of Clinical Immunology, Vol. 15, No. 6, 01.11.1995, p. 349-362.

Research output: Contribution to journalArticle

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