HLA-A2-restricted T-cell epitopes specific for prostatic acid phosphatase

被引:42
|
作者
Olson, Brian M. [2 ]
Frye, Thomas P. [2 ]
Johnson, Laura E. [2 ]
Fong, Lawrence [3 ]
Knutson, Keith L. [4 ]
Disis, Mary L. [5 ]
McNeel, Douglas G. [1 ,2 ]
机构
[1] Univ Wisconsin, Wisconsin Inst Med Res, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Med, Madison, WI 53792 USA
[3] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA
[4] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA
[5] Univ Washington, Div Med Oncol, Tumor Vaccine Grp, Seattle, WA 98195 USA
关键词
CTL; Prostatic acid phosphatase (PAP); HLA-A2; ELISPOT; Epitope; IMMUNOLOGICAL EFFICACY; CANCER IMMUNOTHERAPY; DENDRITIC CELLS; SIPULEUCEL-T; ANTIGEN; PEPTIDE; HLA-A2; TISSUE; IMMUNIZATION; LYMPHOCYTES;
D O I
10.1007/s00262-010-0820-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prostatic acid phosphatase (PAP) has been investigated as the target of several antigen-specific anti-prostate tumor vaccines. The goal of antigen-specific active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+ effector T cells. The identification of PAP-specific CD8+ T-cell epitopes should provide a means of monitoring the immunological efficacy of vaccines targeting PAP, and these epitopes might themselves be developed as vaccine antigens. In the current report, we hypothesized that PAP-specific epitopes might be identified by direct identification of pre-existing CD8+ T cells specific for HLA-A2-restricted peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11 nonamer peptides derived from the amino acid sequence of PAP were used as stimulator antigens in functional ELISPOT assays with peripheral blood mononuclear cells from 20 HLA-A2+ patients with prostate cancer or ten healthy blood donors. Peptide-specific T cells were frequently identified in both groups for three of the peptides, p18-26, p112-120, and p135-143. CD8+ T-cell clones specific for three peptides, p18-26, p112-120, and p299-307, confirmed that these are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic mice immunized with a DNA vaccine encoding PAP developed epitope-specific responses for one or more of these three peptide epitopes. We propose that this method to first identify epitopes for which there are pre-existing epitope-specific T cells could be used to prioritize MHC class I-specific epitopes for other antigens. In addition, we propose that the epitopes identified here could be used to monitor immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify potentially therapeutic immune responses.
引用
收藏
页码:943 / 953
页数:11
相关论文
共 50 条
  • [11] T-CELL RECOGNITION OF AN HLA-A2-RESTRICTED EPITOPE DERIVED FROM A CLEAVED SIGNAL SEQUENCE
    GUEGUEN, M
    BIDDISON, WE
    LONG, EO
    JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (05): : 1989 - 1994
  • [12] Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies
    Brossart, P
    Heinrich, KS
    Stuhler, G
    Behnke, L
    Reichardt, VL
    Stevanovic, S
    Muhm, A
    Rammensee, HG
    Kanz, L
    Brugger, W
    BLOOD, 1999, 93 (12) : 4309 - 4317
  • [13] Enhanced humoral and HLA-A2-restricted dengue virus-specific T-cell responses in humanized BLT NSG mice
    Jaiswal, Smita
    Pazoles, Pamela
    Woda, Marcia
    Shultz, Leonard D.
    Greiner, Dale L.
    Brehm, Michael A.
    Mathew, Anuja
    IMMUNOLOGY, 2012, 136 (03) : 334 - 343
  • [14] Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma
    Wang, Zhiwei
    Ran, Ling
    Chen, Chunxia
    Shi, Ranran
    Dong, Yu
    Li, Yubing
    Zhou, Xiuman
    Qi, Yuanming
    Zhu, Pingping
    Gao, Yanfeng
    Wu, Yahong
    VACCINES, 2021, 9 (10)
  • [15] Altered Peptide Ligands Revisited: Vaccine Design through Chemically Modified HLA-A2-Restricted T Cell Epitopes
    Hoppes, Rieuwert
    Oostvoges, Rimke
    Luimstra, Jolien J.
    Wals, Kim
    Toebes, Mireille
    Bies, Laura
    Ekkebus, Reggy
    Rijal, Pramila
    Celie, Patrick H. N.
    Huang, Julie H.
    Emmelot, Maarten E.
    Spaapen, Robbert M.
    Lokhorst, Henk
    Schumacher, Ton N. M.
    Mutis, Tuna
    Rodenko, Boris
    Ovaa, Huib
    JOURNAL OF IMMUNOLOGY, 2014, 193 (10): : 4803 - 4813
  • [16] Interfering overlapping epitopes contribute to the subdominance of an HLA-A2-Restricted HIV Gag-specific Epitope
    Kan-Mitchell, June
    Nyakeriga, Alice M.
    Salkowitz, Janelle R.
    Costanzo, Margaret C.
    Sidney, John
    Sette, Alessandro
    Ayyavoo, Velpandi
    JOURNAL OF IMMUNOLOGY, 2009, 182
  • [17] Interfering overlapping epitopes contribute to the subdominance of an HLA-A2-restricted HIV Gag-specific epitope
    Kan-Mitchell, J.
    Nyakeriga, A. M.
    Salkowitz, J. R.
    Costanzo, M. C.
    Sidney, J.
    Sette, A.
    Ayyavoo, V.
    RETROVIROLOGY, 2009, 6
  • [18] Relative frequency of specific tumor infiltrating lymphocytes for common HLA-A2-restricted melanoma epitopes.
    Labarriere, N
    Pandolfino, MC
    Raingeard, D
    Diez, E
    Dreno, B
    Jotereau, F
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1997, 109 (03) : 407 - 407
  • [19] Characterizing HLA-A2-restricted CD8+ T-cell epitopes and immune responses to Omicron variants in SARS-CoV-2-inactivated vaccine recipients
    Xiao, Chanchan
    Xiang, Jian
    Wang, Haoyun
    Gao, Wen
    Peng, Tianchan
    Li, Shumin
    Su, Jun
    Chen, Xi
    Gao, Lijuan
    Shi, Ruohu
    Mou, Xinyi
    Yuan, Jun
    Chen, Guobing
    FRONTIERS IN IMMUNOLOGY, 2025, 16
  • [20] Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses
    Didierlaurent, A
    Ramirez, JC
    Gherardi, M
    Zimmerli, SC
    Graf, M
    Orbea, HA
    Pantaleo, G
    Wagner, R
    Esteban, M
    Kraehenbuhl, JP
    Sirard, JC
    VACCINE, 2004, 22 (25-26) : 3395 - 3403