Nucleotide sequence analysis of a human monoclonal antibody TONO-1 with cytotoxic potential for T-leukemia/lymphoma cells

Muneo Numasaki, Kazuyasu Nakamura, Yoshihiro Fukuoka, Hisaaki Saeki, Nobuo Hanai, Toshio Kudo

Research output: Contribution to journalArticlepeer-review

Abstract

A human monoclonal antibody (HuMab) TONO-1 (IgM, λ) recognizes cell surface antigens associated primarily with human T-leukemia/lymphoma cells. In this study, we investigated the reactivity against T-leukemia/lymphoma cells in detail, cytotoxic potential and primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the HuMab TONO-1. Expression of the molecules (TONO-1 Ags) detected by a HuMab TONO-1 was significantly heterogeneous even in the same T-leukemia/lymphoma cell lines HPB-MLT and MOLT-4F. The flow cytometric curves showed an unusual broad-based spread of fluorescence intensity. HuMab TONO-1 was shown to have the ability to kill the T-leukemia/lymphoma cells efficiently in the presence of rabbit complements. However, HuMab TONO-1 did not demonstrate significant antibody-dependent cellular cytotoxic activity. Furthermore, HuMab TONO-1 heavy and light chain variable regions were cloned, sequenced and analyzed. HuMab TONO-1 uses a VH gene member of the VHIV gene family VH71-4, and is productively rearranged with the germ line DH gene DXP′1, and the germ line JH5 gene with multiple somatic mutations. HuMab TONO-1 Vλ belongs to the λ light chain variable subgroup I family and is derived from the Vλlc germ line gene Humlv1042, and germ line gene Jλ1 without somatic mutations. The results reveal that the production of HuMab TONO-1, with cytotoxic potential for human T-leukemia/lymphoma cells, is achieved by rearrangement of the VH71-4/Humlv1042 germ line variable region gene combination, that is associated with the autoimmune repertoire.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalImmunology Letters
Volume75
Issue number3
DOIs
Publication statusPublished - 2001 Jan 15

Keywords

  • Human monoclonal antibody
  • SLE
  • T-leukemia/lymphoma
  • Variable region gene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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