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 language | English |
|---|---|
| Pages (from-to) | 1436-1443 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 2 |
| Publication status | Published - Jul 15 2004 |
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ASJC Scopus subject areas
- Immunology
Cite this
Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute. / Ida, Kazunori; Kawaguchi, Satoshi; Sato, Yuriko; Tsukahara, Tomohide; Nabeta, Yuki; Sahara, Hiroeki; Ikeda, Hideyuki; Torigoe, Toshihiko; Ichimiya, Shingo; Kamiguchi, Kenjiro; Wada, Takuro; Nagoya, Satoshi; Hiraga, Hiroaki; Kawai, Akira; Ishii, Takeshi; Araki, Nobuhito; Myoui, Akira; Matsumoto, Seiichi; Ozaki, Toshihumi; Yoshikawa, Hideki; Yamashita, Toshihiko; Sato, Noriyuki.
In: Journal of Immunology, Vol. 173, No. 2, 15.07.2004, p. 1436-1443.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A*2402 anchor substitute
AU - Ida, Kazunori
AU - Kawaguchi, Satoshi
AU - Sato, Yuriko
AU - Tsukahara, Tomohide
AU - Nabeta, Yuki
AU - Sahara, Hiroeki
AU - Ikeda, Hideyuki
AU - Torigoe, Toshihiko
AU - Ichimiya, Shingo
AU - Kamiguchi, Kenjiro
AU - Wada, Takuro
AU - Nagoya, Satoshi
AU - Hiraga, Hiroaki
AU - Kawai, Akira
AU - Ishii, Takeshi
AU - Araki, Nobuhito
AU - Myoui, Akira
AU - Matsumoto, Seiichi
AU - Ozaki, Toshihumi
AU - Yoshikawa, Hideki
AU - Yamashita, Toshihiko
AU - Sato, Noriyuki
PY - 2004/7/15
Y1 - 2004/7/15
N2 - 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.
AB - 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.
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M3 - Article
VL - 173
SP - 1436
EP - 1443
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -