In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope.
OBJECTIVE
NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells.


METHODS
In vitro stimulation of CD8 or CD4 T cells was determined by IFNgamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFNgamma.


RESULTS
NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2-binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50).


CONCLUSIONS
These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.
Hasegawa
Kosei
K
Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Noguchi
Yuji
Y
Koizumi
Fumihito
F
Uenaka
Akiko
A
Tanaka
Motoyuki
M
Shimono
Michihide
M
Nakamura
Hideo
H
Shiku
Hiroshi
H
Gnjatic
Sacha
S
Murphy
Roger
R
Hiramatsu
Yuji
Y
Old
Lloyd J
LJ
Nakayama
Eiichi
E
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005936:Glucans / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007371:Interferon-gamma / Q000096:biosynthesis; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D005936:Glucans; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D008565:Membrane Proteins; D007371:Interferon-gamma; C009109:pullulan; D002784:Cholesterol