Recognition of HLA-A2-restricted mammaglobin-A-derived epitopes

被引:0
作者
André Jaramillo
Kishore Narayanan
Lacey G. Campbell
Nicholas D. Benshoff
Lonnie Lybarger
Ted H. Hansen
Timothy P. Fleming
Jill R. Dietz
T. Mohanakumar
机构
[1] Washington University School of Medicine,Department of Surgery
[2] Washington University School of Medicine,Department of Genetics
[3] Washington University School of Medicine,Department of Pathology and Immunology
来源
Breast Cancer Research and Treatment | 2004年 / 88卷
关键词
CD8+ T lymphocytes; epitope; HLA-A2; mammaglobin-A; tumor-specific antigen;
D O I
暂无
中图分类号
学科分类号
摘要
A breast cancer-associated antigen, mammaglobin-A, is specifically expressed in 80% of primary breast tumors. The definition of immune responses against this highly expressed breast cancer-specific antigen should be of great value in the development of new therapeutic strategies for breast cancer. Thus, the purpose of this study was to identify HLA-A2-restricted mammaglobin-A-derived epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL). We identified seven mammaglobin-A-derived candidate epitopes that bind the HLA-A2 molecule (Mam-A2.1-7) by means of a HLA class I-peptide binding computer algorithm from the Bioinformatics & Molecular Analysis Section of the National Institutes of Health. Subsequently, we determined that CD8+ CTLs from breast cancer patients reacted to the Mam-A2.1 (83–92, LIYDSSLCDL), Mam-A2.2 (2–10, KLLMVLMLA), Mam-A2.3 (4–12, LMVLMLAAL), Mam-A2.4 (66–74, FLNQTDETL), and Mam-A2.7 (32–40, TINPQVSKT) epitopes using an IFN-c ELISPOT assay. Interestingly, healthy individuals also showed high reactivity to the Mam-A2.2 epitope. Two CD8+ CTL lines generated in vitro against TAP-deficient T2 cells loaded with the candidate epitopes showed significant cytotoxic activity against the Mam-A2.1-4 epitopes. These CD8+CTL lines recognized a HLA-A2+breast cancer cell line expressing the Mam-A2.1 epitope. In addition, DNA vaccination of HLA-A2+/human CD8+ double-transgenic mice with a DNA construct encoding the Mam-A2.1 epitope and the HLA-A2 molecule induced a significant expansion of epitope-specific CD8+ CTLs that recognize the same HLA- A2+/Mam-A2.1+ breast cancer cell line. In conclusion, these results demonstrate the immunotherapeutic potential of mammaglobin-A for the treatment and prevention of breast cancer.
引用
收藏
页码:29 / 41
页数:12
相关论文
共 50 条
  • [41] Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer
    Wei Liu
    Mingxia Zhai
    Zongyin Wu
    Yuanming Qi
    Yahong Wu
    Chao Dai
    Meng Sun
    Lu Li
    Yanfeng Gao
    Amino Acids, 2012, 42 : 2257 - 2265
  • [42] T cell recognition of HLA-A2 restricted tumor antigens is impaired by the oncogene HER2
    Mimura, Kousaku
    Ando, Takashi
    Poschke, Isabel
    Mougiakakos, Dimitrios
    Johansson, C. Christian
    Ichikawa, Jiro
    Okita, Riki
    Nishimura, Michael I.
    Handke, Diana
    Krug, Nancy
    Choudhury, Aniruddha
    Seliger, Barbara
    Kiessling, Rolf
    INTERNATIONAL JOURNAL OF CANCER, 2011, 128 (02) : 390 - 401
  • [43] Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes
    Longmate, J
    York, J
    La Rosa, C
    Krishnan, R
    Zhang, M
    Senitzer, D
    Diamond, DJ
    IMMUNOGENETICS, 2001, 52 (3-4) : 165 - 173
  • [44] Identification of an HLA-A2-restricted CD147 epitope that can induce specific CTL cytotoxicity against drug resistant MCF-7/Adr cells
    Qu, Chuang
    Gao, Shuhui
    Shao, Hongwei
    Zhang, Wenfeng
    Bo, Huabben
    Lu, Xin
    Chen, Tianjiao
    Kou, Jing
    Wang, Yue
    Chen, Gui Si
    Huang, Shulin
    Shen, Han
    ONCOLOGY LETTERS, 2018, 15 (04) : 6050 - 6056
  • [45] Cross-immunizing potential of tumor MAGE-A epitopes recognized by HLA-A*02:01-restricted cytotoxic T lymphocytes
    Huang, Ze-Min
    Jia, Zheng-Cai
    Tang, Jun
    Zhang, Yi
    Tian, Yi
    Ni, Dong-Jing
    Wang, Fang
    Wu, Yu-Zhang
    Ni, Bing
    BMB REPORTS, 2012, 45 (07) : 408 - 413
  • [46] Specific killing of P53 mutated tumor cell lines by a cross-reactive human HLA-A2-restricted P53-specific CTL line
    Würtzen, PA
    Pedersen, LO
    Poulsen, HS
    Claesson, MH
    INTERNATIONAL JOURNAL OF CANCER, 2001, 93 (06) : 855 - 861
  • [48] Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23
    Zeng, Xia
    Nong, Wei-Xia
    Zou, Xiao-Qiong
    Li, Feng
    Ge, Ying-Ying
    Zhang, Qing-Mei
    Luo, Bin
    Huang, Wei
    Zou, Jian-Xia
    Fan, Rong
    Xie, Xiao-Xun
    HUMAN VACCINES & IMMUNOTHERAPEUTICS, 2023, 19 (03)
  • [49] Conservation of HIV-1 T cell epitopes across time and clades: Validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine
    Levitz, Lauren
    Koita, Ousmane A.
    Sangare, Kotou
    Ardito, Matthew T.
    Boyle, Christine M.
    Rozehnal, John
    Tounkara, Karamoko
    Dao, Sounkalo M.
    Kone, Youssouf
    Koty, Zoumana
    Buus, Soren
    Moise, Leonard
    Martin, William D.
    De Groot, Anne S.
    VACCINE, 2012, 30 (52) : 7547 - 7560
  • [50] HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions
    Evans, C
    Bauer, S
    Grubert, T
    Brucker, C
    Baur, S
    Heeg, K
    Wagner, H
    Lipford, GB
    CANCER IMMUNOLOGY IMMUNOTHERAPY, 1996, 42 (03) : 151 - 160