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Journal of Biochemistry Advance Access published online on March 6, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp039
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Effective Induction of Cell Death on Adult T-Cell Leukemia Cells by HLA-DRβ-Specific Small Antibody Fragment Isolated From Human Antibody Phage Library

Satoshi Muraoka1, Yuji Ito1, Masaki Kamimura1, Masanori Baba1, Naomichi Arima2, Yasuo Suda3, Shuhei Hashiguchi1, Masaharu Torikai4, Toshihiro Nakashima4 and Kazuhisa Sugimura1

1 Department of Bioengineering, Faculty of Engineering, Kagoshima University, Korimoto 1-21-40, Kagoshima, Kagoshima 890-0065, Japan.
2 Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, Kagoshima 890-8544, Japan.
3 Nanostructured and Advanced Materials Course, Graduate School of Science and Engineering, Kagoshima University, Korimoto 1-21-40, Kagoshima, Kagoshima 890-0065, Japan.
4 The Chemo-Sero-Therapeutic Research Institute, Kyokushi, Kikuchi, Kumamoto 869-1298, Japan.

Corresponding author: Yuji Ito 1-21-40 Korimoto, Kagoshima 890-0065, Japan Phone: +81-99-285-8346 Fax: +81-99-285-8346 E-mail address: yito{at}be.kagoshima-u.ac.jp

Received December 19, 2008; Accepted February 23, 2009


  Abstract

By a biopanning method using cell sorter, we quickly isolated an antibody phage clone (S1T-A3) specific to human T-lymphotropic virus type 1-carrying T-cell line S1T from a human single chain Fv (scFv) antibody phage library. This scFv antibody bound to HTLV-1-carrying T cell lines including MT-2, MT-4 and M8166 other than S1T, but not to non-HTLV-1-carrying T-cell lymphomas such as Jurkat and MOLT4 cells. Interestingly, this antibody induced the cell death on S1T cells very quickly (less than 30 min). We tried to identify the target molecules by Western blotting and mass spectrometric analysis, revealing that the target antigen was HLA class II DR. The cell death was induced only in dimmer form of scFv (diabody) and at 15-fold lower concentration than that of a fusion protein of scFv and human IgG Fc ((scFv)2-Fc) or anti HLA-DR mouse whole antibody L243. Thus, S1T-A3 diabody is a small antibody fragment with agonistic activity to induce cell death through HLA-DR. This is the first report elucidating that diabody specific to HLA-DR is effective to induce the cell death in T cell malignancy especially adult T cell leukemic cell line.

Key Words: Adult T cell leukemia, Human antibody, scFv, phage library, Diabody


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