Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute

Kazunori Ida, Satoshi Kawaguchi, 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 YoshikawaToshihiko Yamashita, Noriyuki Sato

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1436-1443
Number of pages8
JournalJournal of Immunology
Volume173
Issue number2
DOIs
Publication statusPublished - Jul 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ida, K., Kawaguchi, S., Sato, Y., Tsukahara, T., Nabeta, Y., Sahara, H., Ikeda, H., Torigoe, T., Ichimiya, S., Kamiguchi, K., Wada, T., Nagoya, S., Hiraga, H., Kawai, A., Ishii, T., Araki, N., Myoui, A., Matsumoto, S., Ozaki, T., ... Sato, N. (2004). Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute. Journal of Immunology, 173(2), 1436-1443. https://doi.org/10.4049/jimmunol.173.2.1436