The amyloid-reactive monoclonal anitbody 11-1F4 binds a cryptic epitope on fibrils and partially denatured immunoglobulin light chains and inhibits fibrillogenesis

B. O’nuallain, C. L. Murphy, D. A. Wolfenbarger, Stephen Kennel, Alan Solomon, Jonathan Wall

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)

Abstract

We have previously reported [1] that a murine mAb, designated 11-1F4, prepared against a human Vk4 fibrils (LEN), reacted specifically with AL amyloid, regardless of the V L subgroup of the protein. In order to determine the molecular bases of this interaction, we have utilized a europium-linked immunoabsorbent assay (EuLISA) to measure the interaction of mAb 11-1F4 with light chain-related proteins. These studies show that this antibody does not recognize native k and k chains but, rather, binds with nanomolar affinity to proteins that have been partially denatured, i.e., when coated onto plastic wells used in the assay. EuLISA of peptides derived from proteolytic cleavage of the Vk4 immunogen revealed that the cryptic epitope was located in a region encompassing the first 59 amino acids. Through epitope mapping of synthetic peptides, this site was placed more precisely within the first (N-terminal) 22 residues that comprise the first framework region (FRI) of Ig light chains, and especially involves those located between positions 1 and 4. Additionally, our finding that mAb11-1F4 inhibited at sub-equimolar concentrations de novo V L fibrillogenesis suggests that interaction of this antibody with a partially unfolded amyloidogenic intermediate may act to stabilize the molecule and/or sterically inhibit fibril formation. The discovery that mAb 11-1F4 can prevent fibrillogenesis, as well as accelerate amyloidolysis, has provided new information on its immunoreactivity and therapeutic potential for patients with primary (AL) amyloidosis.

Original languageEnglish (US)
Title of host publicationAmyloid and Amyloidosis
PublisherCRC Press
Pages482-484
Number of pages3
ISBN (Electronic)9781420037494
ISBN (Print)0849335345, 9780849335341
StatePublished - Jan 1 2004

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Immunoglobulin Light Chains
Amyloid
Europium
Epitopes
Immunoglobulin Variable Region
Epitope Mapping
Light
Peptides
Proteins
Antibodies
Plastics
Amino Acids
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

The amyloid-reactive monoclonal anitbody 11-1F4 binds a cryptic epitope on fibrils and partially denatured immunoglobulin light chains and inhibits fibrillogenesis. / O’nuallain, B.; Murphy, C. L.; Wolfenbarger, D. A.; Kennel, Stephen; Solomon, Alan; Wall, Jonathan.

Amyloid and Amyloidosis. CRC Press, 2004. p. 482-484.

Research output: Chapter in Book/Report/Conference proceedingChapter

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