HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ida, K. Articles by Sato, N. Search for Related Content PubMed PubMed Citation Articles by Ida, K. Articles by Sato, N.

Crisscross CTL Induction by SYT-SSX Junction Peptide and Its HLA-A*2402 Anchor Substitute¹

Kazunori Ida^*,, Satoshi Kawaguchi^2,*, Yuriko Sato^*,, Tomohide Tsukahara^*,, Yuki Nabeta^*, Hiroeki Sahara, Hideyuki Ikeda, Toshihiko Torigoe, Shingo Ichimiya, Kenjiro Kamiguchi, Takuro Wada^*, Satoshi Nagoya^*, Hiroaki Hiraga, Akira Kawai^¶, Takeshi Ishii^||, Nobuhito Araki^#, Akira Myoui^**, Seiichi Matsumoto, Toshifumi Ozaki^*, Hideki Yoshikawa^**, Toshihiko Yamashita^* and Noriyuki Sato

Departments of ^* Orthopaedic Surgery and Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan; Marine Biomedical Institute, Sapporo Medical University School of Medicine, Rishirifuji, Hokkaido, Japan; Department of Clinical Research, Division of Orthopedics, National Sapporo Hospital, Sapporo, Japan; ^¶ Department of Orthopaedic Surgery, National Cancer Center Hospital, Tokyo, Japan; ^|| Department of Orthopaedic Surgery, Chiba Cancer Center Hospital, Chiba, Japan; ^# Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; ^** Department of Orthopaedics, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Orthopaedic Surgery, Cancer Institute Hospital, Tokyo, Japan; and ^* Department of Orthopaedic Surgery, Okayama University Medical School, Okayama, Japan

To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24⁺ synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24⁺ synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24⁺ synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.