Peptides that bind specifically to an antibody from a chronic lymphocytic leukemia clone expressing unmutated immunoglobulin variable region genes.
Mol Med
; 19: 245-52, 2013 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-23922242
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
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Región Variable de Inmunoglobulina
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Receptores de Antígenos de Linfocitos B
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Leucemia Linfocítica Crónica de Células B
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Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2013
Tipo del documento:
Article