Peptides that bind specifically to an antibody from a chronic lymphocytic leukemia clone expressing unmutated immunoglobulin variable region genes

Yun Liu, Chelsea D. Higgins, Cathie M. Overstreet, Kanti R. Rai, Nicholas Chiorazzi, Jonathan R. Lai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) is a clonal disease of a subset of human B lymphocytes. Although the cause of the disease is unknown, its development and evolution appear to be promoted by signals delivered when B-cell receptors (BCRs) engage (auto)antigens. Here, using a peptide phage display library of enhanced size and diverse composition, we examined the binding specificity of a recombinant monoclonal antibody (mAb) constructed with the heavy chain and light chain variable domains of a CLL BCR that does not exhibit somatic mutations. As determined by testing the peptides identified in the selected peptide phage pool, this CLL-associated unmutated mAb bound a diverse set of sequences, some of which clustered in families based on amino acid sequence. Synthesis of these peptides and characterization of binding with the CLL-associated mAb revealed that mAb-peptide interactions were generally specific. Moreover, the mAb-peptide interactions were of lower affinities (micromolar KD), as measured by surface plasmon resonance, than those observed with a CLL mAb containing somatic mutations (nanomolar KD) and with immunoglobulin heavy chain variable (IGHV)-mutated antibodies selected by environmental antigens. This information may be of value in identifying and targeting B lymphocytes expressing specific BCRs in CLL patients and healthy subjects with monoclonal B lymphocytosis.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalMolecular Medicine
Volume19
Issue number1
DOIs
StatePublished - 2013

Fingerprint

Immunoglobulin Variable Region
B-Cell Chronic Lymphocytic Leukemia
Clone Cells
Monoclonal Antibodies
Peptides
Antibodies
Genes
B-Lymphocytes
B-Lymphocyte Subsets
Antigens
Peptide Library
Lymphocytosis
Immunoglobulin Heavy Chains
Mutation
Surface Plasmon Resonance
Bacteriophages
Amino Acid Sequence
Healthy Volunteers
Light

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Peptides that bind specifically to an antibody from a chronic lymphocytic leukemia clone expressing unmutated immunoglobulin variable region genes. / Liu, Yun; Higgins, Chelsea D.; Overstreet, Cathie M.; Rai, Kanti R.; Chiorazzi, Nicholas; Lai, Jonathan R.

In: Molecular Medicine, Vol. 19, No. 1, 2013, p. 245-252.

Research output: Contribution to journalArticle

Liu, Yun ; Higgins, Chelsea D. ; Overstreet, Cathie M. ; Rai, Kanti R. ; Chiorazzi, Nicholas ; Lai, Jonathan R. / Peptides that bind specifically to an antibody from a chronic lymphocytic leukemia clone expressing unmutated immunoglobulin variable region genes. In: Molecular Medicine. 2013 ; Vol. 19, No. 1. pp. 245-252.
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