title: Identification of promiscuous KIF20A long peptides bearing both CD4+ and CD8+ T-cell epitopes: KIF20A-specific CD4+ T-cell immunity in patients with malignant tumor.
abstract: OBJECTIVE
  To identify long peptides (LP) derived from a novel tumor-associated antigen (TAA), kinesin family member 20A (KIF20A), which induce tumor-specific T-helper type 1 (TH1) cells and CTLs.
  
  
  METHODS
  We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with KIF20A-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate promiscuous TH1-cell epitopes containing CTL epitopes. Peripheral blood mononuclear cells (PBMC) derived from healthy donors or patients with head-and-neck malignant tumor (HNMT) were used to study the immunogenicity of KIF20A-LPs, and the in vitro cross-priming potential of KIF20A-LPs bearing CTL epitopes. We used HLA-A24 transgenic mice to address whether vaccination with KIF20A-LP induces efficient cross-priming of CTLs in vivo. The TH1-cell response to KIF20A-LPs in HNMT patients receiving immunotherapy with TAA-derived CTL-epitope peptides was analyzed using IFN-γ enzyme-linked immunospot assays.
  
  
  RESULTS
  We identified promiscuous KIF20A-LPs bearing naturally processed epitopes recognized by CD4(+) T cells and CTLs. KIF20A-specific CTLs were induced by vaccination with a KIF20A-LP in vivo. KIF20A expression was detected in 55% of HNMT by immunohistochemistry, and significant frequencies of KIF20A-specific TH1 cell responses were detected after short-term in vitro stimulation of PBMCs with KIF20A-LPs in 50% of HNMT patients, but not in healthy donors. Furthermore, these responses were associated with KIF20A expression in HNMT tissues.
  
  
  CONCLUSIONS
  These are the first results showing the presence of KIF20A-specific TH1 cell responses in HNMT patients and underline the possible utility of KIF20A-LPs for propagation of TH1 cells and CTLs.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomita
authors.forename: Akira
authors.initials: A
authors.lastname: Yuno
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hirayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.forename: Kenta
authors.initials: K
authors.lastname: Kawahara
authors.forename: Junji
authors.initials: J
authors.lastname: Yatsuda
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D016547:Kinesins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C410089:KIF20A protein, human; D010455:Peptides; D016547:Kinesins