Characterization of human CD4 helper T cell responses against Aurora kinase A.
Aurora kinase A (Aurora-A) is a cell cycle-associated serine-threonine kinase that is overexpressed by various types of cancer and is highly associated with poor prognosis. Since the expression of Aurora-A in normal tissues has been shown to be significantly lower as compared to tumor cells, this protein is being considered as a potential tumor-associated antigen for developing immunotherapies. The goal in the present study was to identify CD4 helper T lymphocyte (HTL) epitopes for Aurora-A for the design of T cell-based immunotherapies against Aurora-A-expressing tumors. Synthetic peptides corresponding to potential HTL epitopes were identified from Aurora-A and used to stimulate CD4 T lymphocytes in vitro to generate antigen-specific HTL clones that were evaluated for antigen specificity, MHC restriction and for their ability to interact with Aurora-A-expressing tumor cells. The results show that two peptides (Aurora-A(161-175) and Aurora-A(233-247)) were effective in generating HTL responses that were restricted by more than one MHC class II allele (i.e., promiscuous responses). The CD4 HTL clones were able to directly recognize Aurora-A-expressing tumor cells in an antigen-specific and MHC class II-restricted manner and some of the clones displayed cytolytic activity toward Aurora-A + tumor cells. Both of these peptides were capable of stimulating in vitro T cell responses in patients with bladder cancer.
Kobayashi
Hiroya
H
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
Azumi
Makoto
M
Hayashi
Satoshi
S
Sato
Keisuke
K
Aoki
Naoko
N
Kimura
Shoji
S
Kakizaki
Hidehiro
H
Nagato
Toshihiro
T
Harabuchi
Yasuaki
Y
Tateno
Masatoshi
M
Celis
Esteban
E
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D064096:Aurora Kinase A; D064127:Aurora Kinases; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008285:Major Histocompatibility Complex; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D010455:Peptides / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases