The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins

C. Abatangelo, L. Plotkin, I. Mathov, L. Squiquera, J. Leoni

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Variable domains (V(H)) of all known anti i/I cold agglutinin (CA) heavy chains are codified by the V(H)4-21 gene. While anti-i CAs are the expression of gene rearrangement without mutations represented by amino acid changes, anti-1 CAs present, among others, a frequent somatic mutation of Gly by Asp at position 31. The hydropathy profile calculated for the CDR1H (position 30 to position 35), as well as some adjacent positions of the heavy chain belonging to anti-i and anti-I antibodies, showed the conformational changes accompanying the replacement of Gly by Asp. A MoAb (LP91), which had been obtained in BALB/c mice immunized with a Fabμ fragment from a monoclonal IgMκIIIb anti-I CA (protein KAU), proved capable of inhibiting human adult erythrocyte cryoagglutination by anti-I CAs but not that of fetal erythrocytes by anti-i CAs. Western blot analysis disclosed that such MoAbs recognized a sequential epitope located in the Fd fragment of all anti-I CAs employed in this study. With the purpose of checking whether Asp31 was involved in the epitope recognized by the MoAb, two peptides, D and G, were synthesized which mimicked the CDR1H structure of anti-I and anti-i, respectively; the MoAb only reacted with peptide D by ELISA. Subsequent experimental results indicate that the Gly/Asp mutation could be associated with the diverse specificity presented by these autoantibodies, a change determining a characteristic epitope/idiotope, recognized by LP91 in the CDR1H.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalClinical and Experimental Immunology
Volume104
Issue number1
DOIs
StatePublished - 1996

Keywords

  • CDR1H
  • autoimmunity
  • cold agglutinins
  • public idiotope
  • synthetic peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The frequent mutation Gly/Asp in CDR1H may determine a cross-reactive idiotope in anti-I cold agglutinins'. Together they form a unique fingerprint.

Cite this