A human monoclonal antibody encoded by the v 4-34 gene segment recognises melanoma-associated ganglioside via CDR3 and FWR1

MD Thomas, K Clough, MD Melamed… - Human …, 1999 - content.iospress.com
MD Thomas, K Clough, MD Melamed, FK Stevenson, CJ Chapman, MB Spellerberg…
Human antibodies, 1999content.iospress.com
A heterohybridoma cell line producing the human monoclonal antibody (MoAb) MDT. 1 has
been established. The heavy chain of MoAb MDT. 1 is encoded by the VH gene segment V
4-34 (previously designated VH 4-21), and the light chain is encoded by the Vκ1-L12a gene
segment, both in germline configuration. MDT. 1 has reactivity against lipid A, double-and
single-stranded DNA, red blood cell associated i antigen, and ganglioside antigens. In a
panel of tumour cell lines, MDT. 1 reacted specifically with melanoma cells and other tumour …
Abstract
A heterohybridoma cell line producing the human monoclonal antibody (MoAb) MDT. 1 has been established. The heavy chain of MoAb MDT. 1 is encoded by the V H gene segment V 4-34 (previously designated V H 4-21), and the light chain is encoded by the Vκ1-L12a gene segment, both in germline configuration. MDT. 1 has reactivity against lipid A, double-and single-stranded DNA, red blood cell associated i antigen, and ganglioside antigens. In a panel of tumour cell lines, MDT. 1 reacted specifically with melanoma cells and other tumour cells of neuroectodermal origin. Cellular recognition appears to be via tumour-associated ganglioside antigens, and may involve the minimal essential epitope NeuNacα2→ 3Galβ1→-4Glc-. Binding to ganglioside antigen is inhibited by the monoclonal anti-idiotypic antibody 9G4. Since the 9G4 idiotope is located in framework region 1 (FWR1) of V 4-34-encoded antibodies, this region is likely to be involved, either directly or indirectly, in ganglioside binding. The complementarity-determining region 3 (CDR3) of MDT. 1 is arginine rich, with five out of 12 residues being arginine and these residues are candidates for interaction with the negatively charged ganglioside. The ability of MoAb MDT. 1 to recognise ganglioside antigens is associated with potentially useful anti-tumour activity.
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