Dendritic cells pulsed with gp96-peptide complexes derived from human hepatocellular carcinoma (HCC) induce specific cytotoxic T lymphocytes.
Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APCs) capable of activating immune responses. Different forms of tumor antigens have been used to load DCs to initiate tumor-specific immune responses. Heat shock proteins (HSPs) are considered natural adjuvants which have the ability to chaperone peptides associated with them presented efficiently by interaction with professional APCs through specific receptors. In the present study, we used HSP, gp96-peptide complexes, derived from human hepatocellular carcinoma (HCC) cells as antigens for pulsing DCs. We found that gp96-peptide complexes derived from HCC cells induced the maturation of DCs by enhancing expression of human leukocyte antigen class II, CD80, CD86, CD40, and CD83. The matured DCs stimulated a high level of autologous T cell proliferation and induced HCC specific cytotoxic T lymphocytes, which specifically killed HCC cells by a major histocompatability complex (MHC) class I restricted mechanism. These findings demonstrate that DCs pulsed with gp96-peptide complexes derived from HCC cells are effective in activating specific T cell responses against HCC cells.
Wang
X H
XH
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. China.
Qin
Y
Y
Hu
M H
MH
Xie
Y
Y
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051940:B7-2 Antigen; D019013:CD40 Antigens; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D000097802:CD83 Antigen; C497964:CD86 protein, human; C052646:sarcoma glycoprotein gp96 rejection antigens